Compositions and methods for application over skin

ABSTRACT

Disclosed herein are compositions that can form a covering, layer, film, device, and/or prosthetic skin that can be comfortably worn to provide skin barrier function, skin hydration and therapeutic and aesthetic benefits. The present invention provides novel compositions that have low tackiness and form quickly, resulting in a wearable, comfortable (maintains temperature and humidity), breathable, thin, optically invisible, cosmetically elegant, flexible, stretchable, elastic and body-movement conforming, yet long-lasting covering, layer, film, device, and/or prosthetic skin on the skin or any other body surface. The present invention provides novel compositions that can form a covering, layer, film, device, and/or prosthetic skin that works for extended periods in excess of about 24 hours, while retaining function during and after exercising, showering and swimming (in sea-water, fresh water and chlorinated water), steam room (heat at high humidity), and sauna (heat at low humidity).

CROSS REFERENCES TO RELATED APPLICATIONS

The present application is a continuation of U.S. application Ser. No.15/774,350, filed Nov. 9, 2016, which is a U.S. national stageapplication of International Patent Application No. PCT/US2016/061150,filed Nov. 9, 2016, which claims priority to U.S. Provisional PatentApplication No. 62/252,903, filed on Nov. 9, 2015, each of which isincorporated herein by reference in its entirety.

BACKGROUND OF THE INVENTION

Skin function, e.g., skin barrier function, is critical to protectingthe body from physical injury and environmental factors, regulating skinhydration, regulating body temperature, providing protection frompathogenic invasions, and appearance. When skin is damaged, its abilityto serve as an effective barrier is compromised, thus enabling externalirritants and potentially pathogenic organisms to enter a subject. Inaddition, damaged skin can allow for increased transepidermal water losswhen moisture present in the body is allowed to travel directly to thesurface of the skin where it evaporates, leading to decreased skinhydration (e.g., dry, irritated skin), and loss of skin elasticity.

Skin hydration has been shown to significantly improve skin propertiesand quality of life for individuals with many conditions of compromisedskin barrier function such as dermatitis and psoriasis (see, e.g.,Guidelines of care for the management of atopic dermatitis, J. Am. Acad.Dermatol., 2014 71(1): 116-32; Guidelines of care for the management ofpsoriasis and psoriatic arthritis, J. Am. Acad. Dermatol. 2009,60(4):643-59). However, individuals with such conditions still mainlyrely on the use of occlusive dressings (see, e.g., Hwang et al.,Internat. J. Dermatol. 2001, 40(3):223-231), often in combination withtopical ointments and/or moisturizers. For example, emollient basedmoisturizers increase hydration of the keratin in the stratum corneumand help to reduce scaling, therefore, are often considered an adjuvanttherapy and an essential part of the management of such conditions.Occlusive dressings, topical ointments and moisturizers are a valuablefirst-line treatment, as skin hydration provides transient relief fromirritation caused by transepidermal water loss. Skin hydration furtherleads to improved barrier function, as stratum corneum hydration makesthe epidermis more resistant to external stressors and reduces theinduction of other undesirable conditions such as the Koebner phenomenatriggered by excoriation or maceration and infectious foci due toStreptococcus pyogenes. However, current occlusive dressings are oftendesigned to exclude both oxygen and water, and thereby cutting offskin's oxygen access while providing skin hydration.

Occlusive dressings, topical ointments and/or moisturizers are oftencumbersome, making routine activity for the individual difficult andresulting in poor patient compliance using such dressings, ointmentsand/or moisturizers. In addition, occlusive dressings, topical ointmentsand/or moisturizers often require multiple applications per day to beeffective because they are readily worn off. Moreover, emollient basemoisturizers can cause side effects, such as irritant dermatitis,allergic contact dermatitis, allergy to formula constituents, stinging,cosmetic acne, and other undesired effects. Therefore, it is desirableto find alternative methods of treating conditions of compromised skinbarrier function that are both effective and without undesirable sideeffects.

The design and adoption of a wearable, skin-conforming material posesseveral fundamental challenges. First, the material must be safely wornon skin without causing skin irritations and/or sensitizations. Second,the materials must adhere to skin, while providing a breathable, butprotective, interface to the environment. Third, the material mustpossess mechanical properties that accommodate normal skin's mechanicalresponses to motion while reinforcing inherent skin tension and elasticrecoil. Fourth, the material should preferably mimic, or at least notsignificantly interfere with, the appearance of normal, healthy skin fora wide range of individual skin types. Examples of appearances ofnormal, healthy skin, such as lack of scaling, redness, and unevennesssuch as bumps and/or large pores, are described in Igarashi et al, TheAppearance of Human Skin: A Survey, Foundations and Trends® in ComputerGraphics and Vision, 2007 3(1):1-95.

There are commercially available, pre-formed, skin adherent wounddressings currently on the market, such as silicone wound dressing(e.g., Cica-Care®, Smith and Nephew, Andover, Mass.) and acrylic wounddressing (e.g., Tegaderm™, 3M, St. Paul, Minn.). However, suchpre-formed wound dressings are of fixed area and size, cumbersome,visually noticeable, and do not provide sufficient flexibility anddurability required by routine daily activities.

The 3M Company provides a “Liquid Bandage” product that claims to offerbreathable, waterproof protection to keep out dirt and germs. However,such Liquid Bandages do not provide sufficient flexibility anddurability required by routine daily activities, often have shiny/glossyappearances, and suffer from greatly compromised mechanically integrityand adhesiveness upon rubbing.

Yu et al. (United States Patent Publication 20130078209) disclosecompositions for treating conditions of compromised skin barrierfunction such as dermatological disorders and post-laser, light orchemical-treatment management. However, such compositions are still notas durable as desired, and require more than one application per day.

Accordingly, there remains a need for compositions, devices and methodsfor modifying skin function that form quickly and that are thin,durable, non-invasive, easy to use, and with skin-like properties.

SUMMARY OF THE INVENTION

The present invention is based, at least in part, on the discovery ofdurable, natural looking, non-invasive compositions, and methods forusing such compositions in treating conditions of compromised skinbarrier function. The present invention provides safe compositions thatcan form a covering, a layer, a film, a device, or a prosthetic skin,which allows enhancement and/or reestablishment of one or more skinbarrier functions.

The present compositions are distinct from prior compositions in thatthe layer formed by the present compositions have low tackiness and formquickly, resulting in a wearable, comfortable (maintains temperature andhumidity similar to normal, healthy skin), breathable, thin, opticallyinvisible, cosmetically elegant, flexible, stretchable, elastic andbody-movement conforming, yet long-lasting covering, layer, film, ordevice on the outside of the body (e.g., over skin or any other bodysurface). The present inventions provide novel compositions that arelonger lasting and perform better than prior compositions, particularlyduring more demanding activities, for example, exercising, showering andswimming (in sea-water, fresh water or chlorinated water), steam room(heat at high humidity), and sauna (heat at low humidity).

In particular, the covering, layer, film or device formed from thecompositions disclosed herein regulates transdermal transport propertiesof skin. In one aspect, the covering, layer, film or device helpsmaintain skin hydration by reducing water vapor loss from the body. Inanother aspect, the covering, layer, film or device helps protect thebody from external assaults, such as environmental factors (e.g., heat,cold, wind, water, humidity, bodily fluids (e.g., blood, pus/liquorpuris, urine, saliva, sputum, tears, semen, milk, or vaginal secretion),sebum, saline, seawater, soapy water, detergent water, or chlorinatedwater), pathogens, allergens, and pruritogens. In another aspect, thecovering, layer, film or device helps maintain conditions conducive toskin repair during new skin layer formation such as wound-healing thatminimize scar formation. In another aspect, the covering, layer, film ordevice is used to treat conditions of compromised skin barrier function,including dermatological disorders, skin conditions, and wounds. Inanother aspect, the covering, layer, film or device is used to treatsymptoms of conditions of compromised skin barrier function, such asitchy skin, dry skin, crusting, blistering, or cracking skin,dermatitis, skin edema, skin lesion formation. In another aspect, thecovering, layer, film or device is used to deliver an agent to a subjectto treat a condition of compromised skin barrier function, or to treat asymptom of such a condition.

The covering, layer, film or device formed by the present compositionsis unobtrusive to normal activities of the wearer and is convenient(only one application is required for about 24 hours or more, up toabout a week), affording localized and prolonged skin hydration andother therapeutic, aesthetic, and/or cosmetic benefits.

The covering, layer, film or device formed by the present compositionshas the appearance of normal, healthy skin of the subject, thusconveying cosmetic benefits by masking, concealing, covering, orreducing the appearance of conditions of compromised skin barrierfunction, symptoms of compromised skin barrier function, and/or skinimperfections. The covering, layer, film or device formed by the presentcompositions may further comprise various colors, pearlescents, patternsor designs, thus conveying make up, cosmetic, aesthetic, and/ordecorative benefits.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a chart illustrating the durability of layers formed fromP1-016/P2-004 or a commercial product at about 24 hour time point.

FIG. 2 is a chart illustrating the set-to-touch times of layers formedfrom P1-016/P2-004 or a commercial product.

FIG. 3 is a chart illustrating Set-to-Touch Time and Tack-Free Timecomparing compositions P1-017/P2-004 to P1-023/P2-004, ranked based onhydride-to-vinyl mole ratio within the first part.

FIG. 4 is a chart illustrating Adhesion Peel Force per unit lengthcomparing compositions P1-017/P2-004 to P1-023/P2-004, ranked based onhydride-to-vinyl mole ratio within the first part.

FIG. 5 is a photoset illustrating in-vivo film resistance againstrubbing of the test composition P1-030/P2-021 (full coverage coloredfilm) and P1-028/P2-004 (transparent colored film) on skin.

FIG. 6 is a chart illustrating clinical evaluation of in-vivo Durabilityafter 6 hours and 24 hours of P1-016/P2-004 on skin.

FIG. 7A is a chart illustrating in-vivo optical evaluation of colorL*a*b* scales on test formulation on forearm skin, comparinginvisibility of composition P1-016/P2-004 with the commerciallyTegadermTM product (3M).

FIG. 7B is a chart illustrating in-vivo optical evaluation of normalizedvalues of color L*a*b* scales on test formulation to the values onforearm skin, comparing invisibility of composition P1-016/P2-004 withthe commercially Tegaderm™ product (3M).

FIG. 8 is a photoset illustrating in-vivo evaluation of skin surfacemodulation achieved by P1-016/P2-004: (top) on both under eye areas of amale subject, (middle) on both under eye areas of a female subject,(bottom) on both laugh line areas of a female subject.

FIG. 9 is a photoset illustrating in-vivo evaluation of opticalmodification of skin achieved by P1-030/P2-021: (top) on the coverage ofnatural hyperpigmentation, (bottom) on the coverage of tattoo.

FIG. 10 is a photoset illustrating the incorporation ofstimuli-responsive components into the test composition on skin. (Left)Composition P1-029/P2-004 includes graphene, and (Right) compositionP1-028/P2-004 includes pH-sensitive dye.

FIG. 11 is a photoset illustrating in-vivo barrier protection againstwater penetration to demonstrate the waterproof property of the testcomposition P1-016/P2-004 on skin.

FIG. 12 is a chart illustrating in-vitro barrier evaluation againstnickel contact comparing composition P1-016/P2-004 (right side) againstcontrol (left side with no test composition). The control (left)displayed color change to pink indicating a direct contact to nickel. Incontrast, the right side with the test article P1-016/P2-004 displayedno color change, due to the barrier protection of the film againstnickel contact.

FIG. 13 is a chart illustrating in-vitro barrier evaluation against UVradiation comparing P1-026/P2-004 against control blank and againstover-the-counter SPF 50 spray (Banana Boat).

FIG. 14A is a chart illustrating water vapor transmission comparingP1-016/P2-004 (right side) at different thicknesses against control(left side with no test composition).

FIG. 14B is a chart illustrating the calculation of water vaportransmission rate based on P1-016/P2-004 (right side) at differentthicknesses.

FIG. 15 is a chart illustrating clinical evaluation of in-vivoTransepidermal Water Loss (TEWL) of composition P1-016/P2-004 on skinafter 2, 6, and 24 hours by Evaporimeter measurement.

FIG. 16A is a chart illustrating accumulated transdermal delivered dose(from receptor fluid) of triamcinolone acetonide after 1, 2, 4, 6, 8,and 24 hours from the topical formulations comparing among 0.1%triamcinolone acetonide lotion (TA) (from Versa Pharma), P1-016/P2-004layered on top of 0.1% TA, and P1-027/P2-004.

FIG. 16B is a chart illustrating accumulated delivered dose oftriamcinolone acetonide in the tape strippings after 24 hours from thetopical formulations comparing among 0.1% triamcinolone acetonide lotion(TA) (from Versa Pharma), P1-016/P2-004 layered on top of 0.1% TA, andP1-027/P2-004.

FIG. 16C is a chart illustrating accumulated delivered dose oftriamcinolone acetonide in the epidermal, dermal, and receptor fluidafter 24 hours from the topical formulations comparing among 0.1%triamcinolone acetonide lotion (TA) (from Versa Pharma), P1-016/P2-004layered on top of 0.1% TA, and P1-027/P2-004.

FIG. 17 is an exemplary form used for clinical measurement of PsoriasisArea and Severity Index (PASI) Score.

FIG. 18A is a chart illustrating clinical improvement in eczema severityby IGA after the application of composition P1-016/P2-004 over a periodof 30 days.

FIG. 18B is a chart illustrating improvement of clinical signs inerythema after the application of composition P1-016/P2-004 over aperiod of 30 days.

FIG. 18C is a chart illustrating improvement of clinical signs inpapulation after the application of composition P1-016/P2-004 over aperiod of 30 days.

FIG. 18D is a chart illustrating improvement of clinical signs inexcoriation after the application of composition P1-016/P2-004 over aperiod of 30 days.

FIG. 18E is a chart illustrating improvement of clinical signs inlichenification after the application of composition P1-016/P2-004 overa period of 30 days.

FIG. 18F is a chart illustrating improvement of clinical signs inoozing/crusting after the application of composition P1-016/P2-004 overa period of 30 days.

FIG. 18G is a chart illustrating improvement of clinical signs inpruritus after the application of composition P1-016/P2-004 over aperiod of 30 days.

FIG. 18H is a chart illustrating improvement of several clinical signsof a subject's upper leg area after the application of compositionP1-016/P2-004 over a period of 30 days.

FIG. 18I is a chart illustrating improvement of several clinical signsof a subject's neck and shoulder area after the application ofcomposition P1-016/P2-004 over a period of 30 days.

DETAILED DESCRIPTION OF THE INVENTION

Disclosed herein are compositions that can form a covering, layer, film,device, and/or prosthetic skin over the skin that have low tackiness andform quickly, resulting in a wearable, comfortable (maintainstemperature and humidity similar to normal, healthy skin), breathable,thin, optically invisible, cosmetically elegant, flexible, stretchable,elastic and body-movement conforming, yet long-lasting covering, layer,film, device, and/or prosthetic skin, that can be comfortably worn toprovide skin hydration and other therapeutic, aesthetic, and/or cosmeticbenefits.

The present inventions provide novel compositions that are longerlasting and perform better than prior compositions, particularly duringmore demanding activities, for example, exercising, showering andswimming (in sea-water, fresh water or chlorinated water), steam room(heat at high humidity), and sauna (heat at low humidity). An additionalbenefit is that the extended wearability and/or durability of the layerdoes not require repeated applications to sustain its benefits. Thelayer formed can be worn over a period of about 24 hours or more withoutthe need to reapply.

In particular, the layer formed from the compositions disclosed hereinregulates transdermal transport properties of skin, helps maintain skinhydration by providing an additional barrier over skin against watervapor loss from the body into the environment, helps protect the bodyagainst external and internal assaults, such as environmental factors(e.g., heat, cold, wind, water, humidity), bodily fluids (e.g., blood,pus/liquor puris, urine, saliva, sputum, tears, semen, milk, or vaginalsecretion), sebum, saline, seawater, soapy water, detergent water,chlorinated water, pathogens, allergens, and pruritogens, and helpsmaintain conditions conducive to skin repair during new skin layerformation such as wound-healing that minimize scar formation.

In addition to providing increased compliance with a once-daily, or lessfrequent, application of aesthetically pleasing compositions, users ofsuch compositions benefit from the therapeutic effects. The compositionsand methods described herein provide a more attractive alternative tocurrent treatment options for conditions of compromised skin barrierfunction.

The present compositions are suitable for easy topical application toform an aesthetically invisible, elastic, skin-conforming covering,layer, film, device, and/or prosthetic skin, which can be safely worn onthe skin. Materials used in the present compositions are preferablyselected from the US Food and Drug Administration's list of GenerallyRegarded as Safe (GRAS) substances or equivalents thereof, or areotherwise safe for skin and/or body applications.

As used herein, the term “skin” includes body surfaces where normal skinis intact, compromised, or partially or completely lost or removed. Skinfurther includes skin imperfections that are commonly considered to bepart of “skin.” Examples of skin imperfections include wrinkles,blemishes, freckles, acne, moles, warts, lesions, scars, tattoos,bruises, skin disfigurements, birth marks, sun damage, age damage, spots(e.g., aging spots), uneven skin tone, sagging skin, cellulite, stretchmarks, loss of skin elasticity, skin roughness, enlarged pores,hyperpigmentation, telangiectasia, redness, shine, port wine stain (ornevus flammeus, e.g., nevus flammeus nuchae or midline nevus flammeus),and melasma. Skin further includes skin area over which any cosmetic,personal care, medical, paint, or any other foreign material, or acombination thereof, is applied.

As used herein, the term “layer” includes a covering, film, sheet,barrier, coating, membrane, device or prosthetic skin formed on, sprayedon, or spread over a surface. A layer may be, but is not necessarily,continuous. A layer may, but does not necessarily, have substantiallyeven and/or uniform thickness.

As used herein, the terms “compromised skin barrier function,”“compromised skin barrier,” or “compromised skin condition” includeconditions such as dermatological disorders, skin conditions, andwounds.

“Dermatological disorders” include disorders that cause at least onesymptom on the skin of a subject that may require medical treatment.Dermatological disorders may be caused by, among other things,autoimmune disorders and/or environmental factors, such as allergens orchemicals. Examples of symptoms of dermatological disorders include, butare not limited to, itchy skin, dry skin, crusting, blistering, orcracking skin, dermatitis, skin edema, or skin lesion formation.Dermatological disorders include, but are not limited to, eczema,psoriasis, ichthyosis, rosacea, chronic dry skin, cutaneous lupus,lichen simplex chronicus, xeroderma, acne, disease-driven secondarydermatological disorder, and ulcer.

Eczema includes, e.g., atopic eczema, atopic dermatitis, contactdermatitis, phototoxic dermatitis, xerotic eczema (also known asasteatotic eczema, eczema craquele or craquelatum, winter itch, orpruritus hiemalis), seborrheic dermatitis (or seborrhoeic eczema),dyshidrosis (also known as dyshidrotic eczema, pompholyx, vesicularpalmoplantar dermatitis, or housewife's eczema), discoid eczema (alsoknown as nummular eczema, exudative eczema, microbial eczema), venouseczema (also known as gravitational eczema, stasis dermatitis, varicoseeczema), dermatitis herpetiformis (also known as Duhring's Disease),neurodermatitis (also known as lichen simplex chronicus, localizedscratch dermatitis), autoeczematization, and retinoid-induceddermatitis.

Psoriasis includes, e.g., psoriasis vulgaris (also known as plaquepsoriasis), psoriatic erythroderma, pustular psoriasis (including vonZumbusch, Palmoplantar and Acropustulosis psoriasis), drug-inducedpsoriasis, inverse psoriasis, seborrheic-like psoriasis and guttatepsoriasis.

Ichthyosis includes, e.g., ichthyosis vulgaris, acquired ichthyosis,X-linked ichthyosis, congenital ichthyosiform erythroderma, nonbullous(nbCIE), epidermolytic hyperkeratosis (bullous ichthyosis, bCIE),Harlequin type ichthyosis, ichthyosis bullosa of Siemens, ichthyosishystrix, Curth-Macklin type, Hystrix-like ichthyosis with deafness,Lamellar ichthyosis, type 1, Lamellar ichthyosis, type 2, Lamellarichthyosis, type 3, Lamellar ichthyosis, type 4, Lamellar ichthyosis,type 5, CHILD Syndrome, Conradi-Hünermann syndrome, ichthyosisfollicularis with alopecia and photophobia syndrome,Keratitis-ichthyosis-deafness syndrome, Netherton syndrome, Neutrallipid storage disease with ichthyosis, adult Refsum disease, ichthyosisand male hypogonadism, Sjogren-Larsson syndrome, and photosensitivetrichothiodystrophy (IBIDS syndrome).

Rosacea includes, e.g., erythematotelangiectatic rosacea, papulopustularrosacea, phymatous rosacea (e.g., rhinophyma), and granulomatousrosacea.

Cutaneous lupus includes, e.g., acute cutaneous lupus, subacutecutaneous lupus, chronic cutaneous lupus, chilblain lupus erythematosus,discoid lupus erythematosus, lupus erythematosus-lichen planus overlapsyndrome, lupus erythematosus panniculitis, tumid lupus erythematosusand verrucous lupus erythematosus.

Acne includes, e.g., acne vulgaris, acne aestivalis, acne conglobate,acne cosmetic, acne fulminans, acne keloidalis nuchae, acne mechanica,acne medicamentosa (also known as drug-induced acne, e.g., steroidacne), acne miliaris necrotica, acne necrotica, acne rosacea, andhidradenitis suppurativa.

A “disease-driven secondary dermatological disorder” refers to adermatological condition that may require treatment and was caused by oris associated with a non-dermatological disorder. A “non-dermatologicaldisorder” includes disorders not primarily associated with the skin butwhich may result in, be associated with, or have a secondarymanifestation of a skin condition, for example, a disorder of thecirculatory system or metabolism of the subject. Disease-drivensecondary dermatological disorders include, for example, an ulcer causedby diabetes mellitus (e.g., diabetic foot ulcer), a bacterial, viral orfungal infection, cancer, pressure (e.g., a bedsore), blood disorders,conditions affecting the nervous system (e.g., neuropathic ulcers (alsoknown as “mal perforans”)), conditions affecting the nervous system(e.g., arterial insufficiency ulcers (also known as “ischemic ulcers”)or vascular ulcers), and/or a chronic wound.

“Skin conditions” include, but are not limited to, itchy skin, raw skin,dry skin, flaking or peeling skin, blisters on the skin, redness,swelling or inflammation of the skin, and oozing, scabbing or scalingskin. Skin conditions also include compromised skin barrier conditionscaused by laser, light or chemical peel treatment.

“Wounds” include injuries to the skin wherein the skin is torn, cut orpunctured. Wounds include open wounds, for example, abrasions,lacerations, incisions, punctures, avulsions, or amputations. Woundsalso include burn wounds, a type of injury to skin and/or flesh causedby heat, electricity, wind, chemicals, light, radiation or friction.

“Treat,” “treating” and “treatment” include both therapeutic andprophylactic/preventative measures. “Treat,” “treating” and “treatment”further include both disorder modifying treatment and symptomatictreatment. Treatment may ameliorate or cause a reduction in the severityand/or duration of at least one symptom of the conditions of compromisedskin barrier function. Treatment may also cause a complete recovery fromthe conditions of compromised skin barrier function.

“Apply,” “applied” and “application” includes any and all known methodsof contacting or administering compositions of the invention to asubject's skin or body. The application may be by finger, hand, brush,cotton ball, cotton swab, tissue, pad, sponge, roll-on, spatula,dispenser, drops, spray, splash, foam, mousse, serum, spritz, and otherappropriate methods.

“Subject” includes subjects in which the compositions disclosed hereinwould be appropriate for use, particularly animals (e.g., a human).Subjects may further include plants, wherein skin refers to the surfaceover portions of the plant that may benefit from application of thecomposition, such as flowers, leaves, fruits, stems, branches, bark, androots.

“In vitro” means tested or formed not on, in, or over a subject's skinor body.

“Routine daily activities” include instrumental activities of dailyliving, such as feeding (e.g., eating, drinking, taking medications),continence (e.g., urination and defecation), toileting, dressing,bathing (e.g., shower, bath), grooming, physical ambulation (e.g.,walking, using transportation), talking (e.g., using the telephone),preparing food, housekeeping, doing laundry, shopping, and handlingfinances. Examples of such daily activities are described in Lawton andBrody, Assessment of older people: self-maintaining and instrumentalactivities of daily living, Gerontologist 1969 Autumn; 9(3):179-86 andKatz et al., Studies of Illness in the Aged. The Index of ADL: AStandardized Measure of Biological and Psychosocial Function, JAMA 1963Sep. 21; 185:914-9.

“Demanding activities” include activities that generate elevated levelof strain and/or stress on the skin of a subject as compared to thestrain or stress generated by routine daily activities. Examples of suchdemanding activities include exercising, swimming (in sea-water, freshwater or chlorinated water), steam room (heat at high humidity), sauna(heat at low humidity), and other like activities.

Unless otherwise stated, descriptions of any material used as part ofany composition disclosed herein are of such material as an ingredientof the composition prior to mixing, combination and/or reaction of suchmaterial with other ingredient(s) of the composition.

One aspect of the invention is directed to a composition comprising atleast one crosslinkable polymer. A “crosslinkable polymer” refers to apolymer that can physically or chemically interact, or both physicallyand chemically interact, with itself or with other polymers to form alayer on a surface (e.g., skin, leather, glass, plastic, metal) to whichit is applied. “Physically interact” refers to the formation ofnon-covalent interaction (e.g., hydrogen bonds, or electrostatic, polar,ionic, van der Waals, or London forces) between two or more polymerchains. “Chemically interact” refers to the formation of covalent bondsbetween two or more polymer chains. Covalent bonds may be formed throughchemical reactions that occur spontaneously or are initiated by, forexample, catalyst, moisture, heat, pressure, change in pH, or radiation.The crosslinkable polymer(s) may be homopolymer or copolymer, forexample, random copolymer, alternating copolymer, periodic copolymer,statistical copolymer, block copolymer, graft or grafted copolymer, or acombination thereof

In certain embodiments, the composition comprises one or more physicallycrosslinkable polymers such as semi-crystalline polymers, chargedpolymers, polymers with hydrogen-bond capable linkages, or polymerscapable of forming phase-separation networks (e.g.,poly(styrene-butadiene), poly(dimethylsiloxane-ethyleneoxide)). Inpreferred embodiments, the composition comprises one or more physicallycrosslinkable polymers that can form hydrogen-bond crosslinking networksand/or ionic crosslinking networks, non-limiting examples of whichinclude copolymers among two or more of the following: caprolactone,lactide, glycolide, sebacic, adipic, and trimethylene carbonate. Infurther preferred embodiments, the composition comprises one or morebiological crosslinkable polymers, non-limiting examples of whichinclude one or more of the following: protein-based polymers such askeratin, elastin, collagen; or sugar-based polymers such as chitin,chitosan, cellulose, starch; or lipid-based polymers such as ceramide,triglyceride, sphingosine or a combination thereof

In certain embodiments, the composition comprises one or more chemicallycrosslinkable polymers such as polymers containing functional groupscapable of performing addition polymerization, chain-growthpolymerization, step-growth polymerization, ring-opening polymerization,radical polymerization, anionic polymerization, cationic polymerization,condensation polymerization, living polymerization, photopolymerization,radiation polymerization or other chemical reactions that form one ormore chemical bonds. In preferred embodiments, the composition comprisesone or more chemically crosslinkable polymers that can form covalentcrosslinking networks. In further preferred embodiments, the compositioncomprises one or more chemically crosslinkable polymers selected frompolysiloxane, polyethylene oxide, polypropylene oxide, polyurea,polycarbonate, polyglycerol, polyurethane, polyester (including, but notlimited to, polylactic-co-glycolic acid, polycaprolactone, polylacticacid, polyglycolic acid, and polyhydroxybutyrate, polyamide),polysulfone, polyphosphate, polyamine, polyimine, polythiol, polyboron,or a combination thereof

In certain embodiments, the composition comprises one or more bothphysically and chemically crosslinkable polymers. In preferredembodiments, the composition comprises one or more both physically andchemically crosslinkable polymers such as keratin, elastin, collagen, ora combination thereof.

In preferred embodiments, the composition comprises one or morecrosslinkable organopolymer(s). An “organopolymer” refers to a polymerthat includes carbon.

In certain embodiments, the composition comprises: Polymer A) one ormore organopolymer(s) having on average at least two carbon double bonds(i.e., alkenyl-functional group) or at least one carbon triple bond(i.e., alkynyl-functional group) within each molecule; and Polymer B)one or more organopolysiloxane(s) having on average at least twoSi-hydrogen-containing monomer units (Si—H units) within each molecule.

In preferred embodiments, the organopolymer comprisesorganopolysiloxanes, which are polymers based upon the following monomerunits:

and terminal units:

wherein each R₁, R₂, and R^(t) ₁-R^(t) ₆ is independently selected fromhydrogen, C₁₋₂₅ alkyl, C₂₋₂₅ alkenyl, C₂₋₂₅ alkynyl, C₅₋₁₀ aryl,halogen, amino and hydroxy, wherein the C₁₋₂₅ alkyl, C₂₋₂₅ alkenyl,C₂₋₂₅ alkynyl, and C₅₋₁₀ aryl may be optionally substituted with 1 to 3substituents selected from C₁₋₂₅ alkyl, halogen, haloC₁₋₂₅ alkyl, aminoand hydroxy, and wherein n is an integer between 10 and 3000. R₁ and R₂of each monomer unit may be, but are not necessarily the same.

As used herein, “alkyl,” “alkenyl” and “alkynyl” include bothstraight-chain and branched hydrocarbon groups. As used herein, “amino”includes both primary amines such as —NH₂ and secondary or tertiaryamines wherein one or both of the hydrogen atoms have been replaced withan alkyl group. Non-siloxane repeat units may be present in the polymerbackbone of organopolysiloxane.

In preferred embodiments, R^(thd 1) and R^(t) ₄ are alkenyl or alkynyland each R₁, R₂, R^(t) ₂ R^(t) ₃, R^(t) ₅, and R^(t) ₆ is independentlyselected from C₁₋₂₅ alkyl, C₅₋₁₀ aryl, halogen, amino and hydroxy,wherein the C₁₋₂₅ alkyl, C₂₋₂₅ alkenyl, and C₅₋₁₀ aryl may be optionallysubstituted with 1 to 3 substituents selected from C₁₋₂₅ alkyl, halogen,haloC₁₋₂₅ alkyl, amino and hydroxy. In further preferred embodiments,R^(t) ₁ and R^(t) ₄ are alkenyl or alkynyl and each R₁, R₂, R^(t) ₂R^(t) ₃, R^(t) ₅, and R^(t) ₆ is independently C₁₋₂₅ alkyl optionallysubstituted with 1 to 3 substituents selected from halogen or haloC₁₋₂₅alkyl.

In certain embodiments, R^(t) ₁ and R^(t) ₄ are hydrogen and each R₁,R₂, R^(t) ₂ R^(t) ₃, R^(t) ₅, and R^(t) ₆ is independently selected fromC₁₋₂₅ alkyl, C₅₋₁₀ aryl, halogen, amino and hydroxy, wherein the C₁₋₂₅alkyl, and C₅₋₁₀ aryl may be optionally substituted with 1 to 3substituents selected from C₁₋₂₅ alkyl, halogen, haloC₁₋₂₅ alkyl, aminoand hydroxy. In preferred embodiments, each R₁, R₂, and R^(t) ₁-R^(t) ₆is independently selected from hydrogen, C₁₋₂₅ alkyl, C₅₋₁₀ aryl,halogen, amino and hydroxy, wherein the C₁₋₂₅ alkyl, and C₅₋₁₀ aryl maybe optionally substituted with 1 to 3 substituents selected from C₁₋₂₅alkyl, halogen, haloC₁₋₂₅ alkyl, amino and hydroxyl. In a preferredembodiment, the Si—H units in the organopolysiloxane are spaced onaverage by at least about 1 monomer units, about 2 monomer units, about5 monomer units, about 10 monomer units, about 20 monomer units, about40 monomer units, about 200 monomer units, about 400 monomer units,about 1,000 monomer units, or about 2,000 monomer units.

In certain embodiments, the organopolysiloxane is primarily comprised ofsiloxane monomer units, i.e., substantially all of the repeat unitsalong the polymer backbone are siloxane units. In preferred embodiments,the organopolysiloxane comprises greater than 90%, greater than 95%,greater than 98%, or greater than 99% siloxane repeat units along thepolymer backbone.

In certain embodiments, the Si—H to alkenyl (e.g., vinyl) or Si—H toalkynyl molar ratio of the polymers in the composition is about 1:5 toabout 60:1; about 10:1 to about 30:1; or about 20:1 to about 25:1.

In preferred embodiments, the composition comprises: Polymer A) one ormore organopolysiloxane(s) having on average at least two carbon doublebonds or at least one carbon triple bond within each molecule; andPolymer B) one or more organopolysiloxane(s) having on average at leasttwo Si—H units within each molecule.

In preferred embodiments, the composition further comprises one or morereinforcing component(s). In certain embodiments, the reinforcingcomponent is selected from surface treated carbon, silver, mica, zincsulfide, zinc oxide, titanium dioxide, aluminum oxide, clay (e.g.,Al₂O₃, SiO₂), chalk, talc, calcite (e.g., CaCO₃), barium sulfate,zirconium dioxide, polymer beads and silica (e.g., silica aluminates,calcium silicates, or surface treated silica (e.g., fumed silica,hydrated silica, or anhydrous silica)), or a combination thereof. Suchreinforcing components reinforce the physical properties of the layer asdiscussed herein. In preferred embodiments, the reinforcing component issurface treated silica, for example, silica treated withhexamethyldisilazane, polydimethylsiloxane, hexadecylsilane ormethacrylsilane. In further preferred embodiments, the reinforcingcomponent is fumed silica, including fumed silica having been surfacetreated with hexamethyldisilazane.

In certain embodiments, the particles of the reinforcing component havean average surface area of between about 50 and about 500 m²/g. Inpreferred embodiments, the particles of the reinforcing component havean average surface area of between about 100 and about 350 m²/g. Infurther preferred embodiments, the particles of the reinforcingcomponent have an average surface area of between about 135 and about250 m²/g. In certain embodiments, the reinforcing component has anaverage particle diameter of between about 1 nm and about 20 μm. Inpreferred embodiments, the reinforcing component has an average particlediameter of between about 2 nm and about 1 μm, and further preferablybetween about 5 nm and about 50 nm.

In preferred embodiments, the composition comprises about 5 to about 90%by weight Polymer A; about 5 to about 75% by weight Polymer B; and about0 to about 25% by weight reinforcing component. In further preferredembodiments, the composition comprises about 50 to about 90% by weightPolymer A; about 5 to about 30% by weight Polymer B; and about 5 toabout 15% by weight reinforcing component.

In certain embodiments, the organopolysiloxane having carbon double ortriple bonds includes such carbon double or triple bonds at terminalunits of the polymer, in non-terminal monomer units of the polymer, or acombination thereof In preferred embodiments, the organopolysiloxanehaving carbon double or triple bonds includes such carbon double ortriple bonds in non-terminal monomer units of the polymer. In preferredembodiments, the carbon double bond-containing monomer units in theorganopolysiloxane are spaced on average by at least about 40 monomerunits, about 200 monomer units, about 400 monomer units, about 1,000monomer units, or about 2,000 monomer units.

In certain embodiments, the organopolysiloxane having carbon double ortriple bonds has a weight percent of carbon double/triplebond-containing monomer units of between about 0.01 and about 2%, andpreferably, between about 0.03 and about 0.6%. In certain embodiments,the organopolysiloxane having carbon double or triple bonds has a vinylequivalent per kilogram of between about 0.005 and about 0.5, andpreferably, between about 0.01 and about 0.25. An approximate molaramount of the carbon double/triple bonds in the organopolysiloxane canbe calculated based on the average molecular weight of theorganopolysiloxane.

In certain embodiments, the organopolysiloxane having Si—H unitsincludes such Si—H units at terminal units of the polymer, innon-terminal monomer units of the polymer, or a combination thereof. Inpreferred embodiments, the organopolysiloxane having Si—H units includessuch Si—H units in non-terminal monomer units of the polymer. Inpreferred embodiments, the Si—H-containing monomer units in theorganopolysiloxane are spaced on average by at least about 1 monomerunits, about 2 monomer units, about 5 monomer units, about 10 monomerunits, about 20 monomer units, about 40 monomer units, about 200 monomerunits, about 400 monomer units, about 1,000 monomer units, or about2,000 monomer units.

In certain embodiments, the organopolysiloxane having Si—H units has aweight percent of Si—H-containing monomer units of between about 0.003and about 50%, and preferably, between about 0.01 and about 25%. Incertain embodiments, the organopolysiloxane having Si—H units has anSi—H content of between about 0.1 mmol/g and about 20 mmol/g, about 0.5mmol/g and about 10 mmol/g, and preferably, between about 1 mmol/g andabout 5 mmol/g. An approximate molar amount of the Si—H units in theorganopolysiloxane can be calculated based on the average molecularweight of the organopolysiloxane. Average molecular weight, or molarmass, of the ingredients disclosed herein are commonly provided by thesupplier of the ingredients, expressed in units of Dalton (Da) or itsequivalent g/mol.

The term “viscosity” refers to the measure of the resistance of a fluidwhich is being deformed by either shear stress or tensile stress. Theviscosity of the composition affects the thickness, spreadability, andevenness and/or uniformity of the layer formed on a substrate. Viscositymay be reported as either dynamic viscosity (also known as absoluteviscosity, typical units Pa·s, Poise, P, cP) or kinematic viscosity(typical units cm²/s, Stokes, St, cSt), which is the dynamic viscositydivided by density of the fluid measured. Viscosity ranges of theingredients disclosed herein are commonly provided by the supplier ofthe ingredients in units of kinematic viscosity (e.g., cSt), as measuredusing a Rheometer or a Cannon-Fenske Tube Viscometer.

Viscosity of a fluid can be measured in vitro, for example, using arheometer (e.g., linear shear rheometer or dynamic shear rheometer) or aviscometer (also called viscosimeter, e.g., capillary viscometer orrotational viscometer), at an instrument specific strain. For example,Thomas G. Mezger, The Rheology Handbook: For Users of Rotational andOscillatory Rheometers (2nd Ed.), Vincentz Network, 2006, and AmericanSociety for Testing and Materials (ASTM) standards such as ASTMD3835-08, ASTM D2857-95, ASTM D2196-10, and ASTM D2983-09 provideinstructions on how to measure the viscosity of a fluid. Viscosity of afluid is preferably measured in vitro using the Rheometer ViscosityMeasurement Test described herein. Density of the fluid may vary withtemperature or pressure. Unless otherwise specified, all properties ofcompositions, layers and/or devices disclosed herein, includingviscosity, are measured at room temperature (about 25° C.) and about 1atmosphere air pressure.

In certain embodiments, the composition has a viscosity above about 100cP and below about 1,000,000 cP at about 25° C. In certain embodiments,the composition has a viscosity below about 750,000 cP, below about500,000 cP, or below about 250,000 cP at about 25° C. In preferredembodiments, the composition has a viscosity below about 200,000 cP,below about 175,000 cP, below about 150,000 cP, below about 125,000 cP,below about 100,000 cP, or below about 80,000 cP at about 25° C. Incertain embodiments, the composition has a viscosity above about 100 cP,above about 500 cP, or above about 1000 cP at about 25° C. In preferredembodiments, the composition has a viscosity above about 2000 cP, aboveabout 5000 cP, above about 7500 cP, or above about 10,000 cP at about25° C. In further preferred embodiments, the composition has a viscosityabove about 15,000 cP at about 25° C.

In preferred embodiments, the composition comprises: Polymer A) one ormore organopolysiloxane(s) having on average at least twoalkenyl-functional groups and having a viscosity of about 10,000 toabout 2,000,000 cSt at about 25° C.; Polymer B) one or moreorganopolysiloxane(s) having on average at least two Si—H units andhaving a viscosity of about 2 to about 100,000 cSt at about 25° C.; and,optionally, Polymer C) one or more organopolysiloxane(s) having onaverage at least one alkenyl-functional groups and having a viscosity ofabout 0.7 to about 10,000 cSt at about 25° C.

In certain embodiments, the molar ratio of Si—H functional group fromPolymer B to alkenyl-functional group from Polymer A is from about 60:1to about 1:5. In preferred embodiments, the molar ratio of Si—Hfunctional group from Polymer B to alkenyl-functional group from PolymerA is about 45:1 to about 15:1. In certain embodiments, the molar ratioof Si—H functional group from Polymer B to alkenyl-functional group fromPolymer C is from about 60:1 to about 1:5. In preferred embodiments, themolar ratio of Si—H functional group from Polymer B toalkenyl-functional group from Polymer C is about 45:1 to about 15:1. Incertain embodiments, the molar ratio of alkenyl-functional group fromPolymer A to alkenyl-functional group from Polymer C is about 100:1 toabout 1:100. In preferred embodiments, the molar ratio ofalkenyl-functional group from Polymer A to alkenyl-functional group fromPolymer C is about 10:1 to about 1:10.

In certain embodiments, Polymer A has a viscosity between about 10,000and about 2,000,000 cSt at about 25° C. In preferred embodiments,Polymer A has a viscosity above about 20,000, above about 40,000, aboveabout 60,000, above about 80,000, or above about 100,000 cSt at about25° C. In further preferred embodiments, Polymer A has a viscosity aboveabout 125,000 or above about 150,000 cSt at about 25° C. In preferredembodiments, Polymer A has a viscosity below about 1,000,000 cSt, belowabout 500,000 cSt, below about 450,000, below about 400,000, below about350,000, below about 300,000, or below about 250,000 cSt at about 25° C.In further preferred embodiments, Polymer A has a viscosity below about200,000 or below about 180,000 cSt at about 25° C. In further preferredembodiments, Polymer A has a viscosity of about 165,000 cSt at about 25°C.

In certain embodiments, Polymer A has an average molecular weightbetween about 60,000 Da and about 500,000 Da. In preferred embodiments,Polymer A has an average molecular weight above about 72,000 Da, about84,000 Da, about 96,000 Da, or about 100,000 Da. In further preferredembodiments, Polymer A has an average molecular weight above about140,000 Da, or about 150,000 Da. In preferred embodiments, Polymer A hasan average molecular weight below about 200,000 Da, below about 190,000Da, about 180,000 Da, or about 170,000 Da. In further preferredembodiments, Polymer A has an average molecular weight below about160,000 Da. In further preferred embodiments, Polymer A has an averagemolecular weight of about 155,000 Da.

In certain embodiments, Polymer B has a viscosity between about 2 toabout 500,000 cSt at about 25° C. In preferred embodiments, Polymer Bhas a viscosity above about 3 cSt, above about 4 cSt, or above about 12cSt at about 25° C. In further preferred embodiments, Polymer B has aviscosity above about 40 cSt at about 25° C. In preferred embodiments,Polymer B has a viscosity below about 200,000, below about 100,000,below about 50,000, below about 20,000, below about 10,000, below about5,000, below about 2,000, or below about 1,000 cSt at about 25° C. Infurther preferred embodiments, Polymer B has a viscosity below about 500cSt at about 25° C. In further preferred embodiments, Polymer B has aviscosity between about 45 to about 100 cSt at about 25° C.

In certain embodiments, Polymer B has an average molecular weightbetween about 400 and about 500,000 Da. In preferred embodiments,Polymer B has an average molecular weight above about 500 Da, about 800Da, about 1,200 Da, or about 1,800 Da. In further preferred embodiments,Polymer B has an average molecular weight above about 2,000 Da. Inpreferred embodiments, Polymer B has an average molecular weight belowabout 250,000 Da, below about 140,000 Da, below about 100,000 Da, belowabout 72,000 Da, below about 62,700 Da, below about 49,500 Da, belowabout 36,000 Da, or below about 28,000 Da. In further preferredembodiments, Polymer B has an average molecular weight below about17,200 Da. In further preferred embodiments, Polymer B has an averagemolecular weight between about 2,200 Da and 6,000 Da.

In certain embodiments, Polymer C has a viscosity of between about 0.7cSt to about 10,000 cSt at about 25° C. In preferred embodiments,Polymer C has a viscosity of above about 1 cSt, above about 6 cSt, aboveabout 10 cSt, above about 20 cSt, above about 50 cSt, or above about 100cSt at about 25° C. In further preferred embodiments, Polymer C has aviscosity of above about 200 cSt at about 25° C. In preferredembodiments, Polymer C has a viscosity of below about 5,000 cSt, about4,000 cSt, below about 2,000 cSt, or below about 1,000 cSt at about 25°C. In further preferred embodiments, Polymer C has a viscosity of belowabout 500 cSt at about 25° C. In further preferred embodiments, PolymerC has a viscosity of about 250 cSt at about 25° C.

In certain embodiments, Polymer C has an average molecular weightbetween about 180 Da and about 65,000 Da. In preferred embodiments,Polymer C has an average molecular weight above about 500 Da, about 800Da, about 1,500 Da, about 3,000 Da, or about 6,000 Da. In furtherpreferred embodiments, Polymer C has an average molecular weight aboveabout 9,400 Da. In preferred embodiments, Polymer C has an averagemolecular weight below about 50,000 Da, about 45,000 Da, or about 30,000Da. In further preferred embodiments, Polymer C has an average molecularweight below about 17,500 Da. In further preferred embodiments, PolymerC has an average molecular weight of about 10,000 Da.

In preferred embodiments, Polymers A and C are each independentlyselected from vinyl terminated polydimethylsiloxane, vinyl terminateddiphenyl siloxane-dimethylsiloxane copolymers, vinyl terminatedpolyphenylmethylsiloxane, vinylphenylmethyl terminatedvinylphenylsiloxane-phenylmethylsiloxane copolymer, vinyl terminatedtrifluoropropylmethylsiloxane-dimethylsiloxane copolymer, vinylterminated diethyl siloxane-dimethylsiloxane copolymer,vinylmethylsiloxane-dimethylsiloxane copolymer, trimethylsiloxyterminated, vinylmethylsiloxane-dimethylsiloxane copolymers, silanolterminated, vinylmethylsiloxane-dimethylsiloxane copolymers, vinylterminated, vinyl gums, vinylmethylsiloxane homopolymers, vinylT-structure polymers, vinyl Q-structure polymers, unsaturatedorganopolymers (non-limiting examples of which include one or more ofunsaturated fatty alcohols, unsaturated fatty acids, unsaturated fattyesters, unsaturated fatty amide, unsaturated fatty urethane, unsaturatedfatty urea, ceramide, cocetin, lecithin and sphingosine), monovinylterminated polydimethylsiloxanes, vinylmethylsiloxane terpolymers,vinylmethoxysilane homopolymers, vinyl terminated polyalkylsiloxanepolymers, vinyl terminated polyalkoxysiloxane polymers and combinationsthereof In further preferred embodiments, Polymers A and C are eachvinyl dimethicone.

In preferred embodiments, Polymer B is selected from hydride terminatedpolydimethylsiloxane, hydride terminatedpolyphenyl-(dimethylhydrosiloxy)siloxane, hydride terminatedmethylhydrosiloxane-phenylmethylsiloxane copolymer, trimethylsiloxyterminated methylhydrosiloxane-dimethylsiloxane copolymers,polymethylhydrosiloxanes, trimethylsiloxy terminated,polyethylhydrosiloxane, triethylsiloxane,methylhydrosiloxane-phenyloctylmethylsiloxane copolymer,methylhydrosiloxane-phenyloctylmethylsiloxane terpolymer, andcombinations thereof In further preferred embodiments, Polymer B ishydrogen dimethicone.

In certain embodiments, the composition is a two-part compositioncomprising a first part and a second part. In preferred embodiments, thefirst part comprises Polymers A and B. In preferred embodiments, thefirst part further comprises one or more reinforcing component(s). Inpreferred embodiments, the second part comprises Polymer C.

In certain embodiments, the weight ratio of polymers to reinforcingcomponent is about 100:1 to about 1:1. In the preferred embodiments, theweight ratio of polymers to reinforcing component is about 50:1 to about2:1. In further preferred embodiments, the weight ratio of polymers toreinforcing component is about 15:1 to about 3:1. In more preferredembodiments, the weight ratio of polymers to reinforcing component isabout 10:1 to about 4:1. In even more preferred embodiments, the weightratio of polymers to reinforcing component is about 7:1 to about 8:1.

In preferred embodiments, the first part comprises about 5 to about 90%by weight Polymer A; about 5 to about 75% by weight Polymer B; and about0 to about 25% by weight reinforcing component. In further preferredembodiments, the first part comprises about 50 to about 90% by weightPolymer A; about 5 to about 30% by weight Polymer B; and about 5 toabout 15% by weight reinforcing component.

In certain embodiments, the composition further comprises a catalystthat facilitates crosslinking of the one or more crosslinkable polymers.In case of a two-part composition, in certain embodiments, the secondpart further comprises one or more catalyst(s) that facilitatescrosslinking of the one or more crosslinkable polymers. “Catalyst”includes any substance that causes, facilitates, or initiates a physicaland/or chemical crosslinking reaction. The catalyst may or may notundergo permanent physical and/or chemical changes during or at the endof the process. In preferred embodiments, the catalyst is a metalcatalyst capable of initiating and/or facilitating the crosslinking ator below body temperature, for example, Group VIII metal catalysts, suchas platinum, rhodium, palladium, cobalt, nickel, ruthenium, osmium andiridium catalysts, and Group IVA metal catalysts, such as germanium andtin. In further preferred embodiments, the catalyst is a platinumcatalyst, a rhodium catalyst or a tin catalyst. Examples of platinumcatalysts include, for example, platinum carbonylcyclovinylmethylsiloxane complexes, platinumdivinyltetramethyldisiloxane complexes, platinumcyclovinylmethylsiloxane complexes, platinum octanaldehyde/octanolcomplexes, and other Pt(0) catalysts such as Karstedt's catalyst,platinum-alcohol complexes, platinum-alkoxide complexes, platinum-ethercomplexes, platinum-aldehyde complexes, platinum-ketone complexes,platinum-halogen complexes, platinum-sulfur complexes, platinum-nitrogencomplexes, platinum-phophorus complexes, platinum-carbon double-bondcomplexes, platinum carbon triple-bond complexes, platinum-imidecomplexes, platinum-amide complexes, platinum-ester complexes,platinum-phosphate ester complexes, platinum-thiol ester complexes,platinum lone-pair-electron complexes, platinum-aromatic complexes,platinum π-electron complexes, and combinations thereof. Examples ofrhodium catalyst include tris (dibutylsulfide) rhodium trichloride andrhodium trichloride hydrate. Examples of tin catalysts include tin IIoctoate, tin II neodecanoate, dibutyltin diisooctylmaleate,Di-n-butylbis(2,4 pentanedionate)tin, di-n-butylbutoxychlorotin,dibutyltin dilaurate, dimethyltin dineodecanoate,dimethylhydroxy(oleate)tin and tin II oleate. In preferred embodiments,the catalyst is platinum catalyst. In further preferred embodiments, thecatalyst is platinum divinyltetramethyldisiloxane complexes.

In preferred embodiments, the composition comprises about 0.001 to about1% by weight (i.e., about 10 ppm to about 10,000 ppm), preferably about0.005 to about 0.05% by weight (i.e., about 50 ppm to about 500 ppm)catalyst. In further preferred embodiments, the composition comprisesabout 0.01 to about 0.03% by weight catalyst.

In certain embodiments, the composition is a two-part composition,comprising a first part comprising polymer(s) A and Polymer B; and asecond part comprising polymer(s) C and one or more catalyst(s).

In certain embodiments, the composition is a two-part composition,comprising a first part comprising polymer(s) A and polymer(s) C and oneor more catalyst(s); and a second part comprising Polymer B.

In certain embodiments, the composition is a two-part composition,comprising a first part comprising polymer(s) A and one or morecatalyst(s); and a second part comprising Polymer B and polymer(s) C.

In certain embodiments, the composition is a two-part composition,comprising a first part comprising Polymer B and polymer(s) C; and asecond part comprising polymer(s) A and one or more catalyst(s).

In preferred embodiments, the second part comprises about 0.005 to about0.05% by weight catalyst. In further preferred embodiments, the secondpart comprises about 0.01 to about 20% by weight Polymer C; and about0.005 to about 0.05% by weight catalyst. In further preferredembodiments, the second part comprises about 0.5 to about 10% by weightPolymer C; and about 0.01 to about 0.03% by weight catalyst.

In certain embodiments, the first part is applied over skin prior toapplication of the second part, and a layer is formed after the secondpart is applied over the first part. In certain embodiments, the secondpart is applied over skin prior to application of the first part, and alayer is formed after the first part is applied over the second part. Incertain embodiments, the first part is applied over skin together withthe second part, and a layer is formed after both compositions areapplied. In certain embodiments, the first part and the second part aremixed together and then applied over the skin, and a layer is formedafter the mixture is applied. In preferred embodiments, the first partis gently spread over an area of skin of the subject, the second part isgently spread over the first part, covering the entire first part area.

In certain embodiments, the ratio of weight or volume amount of thefirst part to the second part is about 5:1 to about 1:20. In preferredembodiments, the ratio of weight or volume amount of the first part tothe second part is about 2:1 to about 1:2. In further preferredembodiments, the ratio of weight or volume amount of the first part tothe second part is about 1:1.

Anhydrous compositions generally have longer shelf-life than emulsionswith similar ingredients, without the need for preservatives againstbacteria or mold. “Anhydrous” as used herein refers to containing as aningredient less than about 10%, less than about 5%, less than about 2%,less than about 1%, or less than about 0.1% water. In some embodiments,the composition is anhydrous. In some embodiments, the composition is anemulsion. In some embodiments, the composition is a dispersion. In someembodiments, the composition is a suspension. In some embodiments, thecomposition is a paste. In some embodiments, the composition is asemi-solid. In some embodiments, the composition is an ointment. In someembodiments, the composition is a cream. In some embodiments, thecomposition is a serum. In some embodiments, the composition is alotion. In some embodiments, the composition is a patch. In certainembodiments, the composition can be spread, sprayed, stenciled stamped,patterned, patched, transferred, layered, covered or spritzed over skin.

In certain embodiments, the first part is anhydrous. Alternatively, thefirst part is an emulsion. In certain embodiments, the first part can bespread, sprayed or spritzed over skin.

In certain embodiments, the second part is anhydrous. Alternatively, thesecond part is an emulsion. In certain embodiments, the second part canbe spread, sprayed or spritzed over skin.

In certain embodiments, the first part has a viscosity above about 100cP, above about 500 cP, or above about 1000 cP at about 25° C. Inpreferred embodiments, the first part has a viscosity above about 2000cP, above about 5000 cP, above about 7500 cP, or above about 10,000 cPat about 25° C. In further preferred embodiments, the first part has aviscosity above about 15,000 cP at about 25° C. In certain embodiments,the first part has a viscosity below about 1,000,000 cP, below about750,000 cP, below about 500,000 cP, or below about 250,000 cP at about25° C. In preferred embodiments, the first part has a viscosity belowabout 200,000 cP, below about 175,000 cP, below about 150,000 cP, belowabout 125,000 cP, below about 100,000 cP, or below about 80,000 cP atabout 25° C.

In certain embodiments, the second part has a viscosity above about 100cP, above about 500 cP, or above about 1000 cP at about 25° C. Inpreferred embodiments, the second part has a viscosity above about 2000cP, above about 5000 cP, above about 7500 cP, or above about 10,000 cPat about 25° C. In further preferred embodiments, the second part has aviscosity above about 15,000 cP at about 25° C. In certain embodiments,the second part has a viscosity below about 1,000,000 cP, below about750,000 cP, below about 500,000 cP, below about 250,000 cP, below about200,000 cP, or below about 175,000 cP at about 25° C. In preferredembodiments, the second part has a viscosity below about 150,000 cP,below about 125,000 cP, or below about 100,000 cP at about 25° C. Infurther preferred embodiments, the second part has a viscosity belowabout 80,000 cP at about 25° C.

In certain embodiments, the composition further comprises one or moreadditives. In certain embodiments, the first part and/or the second partfurther independently comprise(s) one or more additives. Suitableadditives include, but are not limited to, feel modifiers, tackmodifiers, spreadability enhancers, diluents, adhesion modifiers,volatile siloxanes, emulsifiers, emollients, surfactants, thickeners,solvents, film formers, humectants, preservatives, pigments, skinpermeation enhancers, optic modifiers, gas transport modifiers, liquidtransport modifiers, pH modifiers, sensitizing modifiers, aestheticmodifiers, and a combination thereof. Additional suitable additives aredisclosed in the International Nomenclature Cosmetic Ingredient (INCI)dictionary, which is incorporated herein by reference in its entirety.In preferred embodiments, the emulsifiers are alkoxydimethicone,alkyldimethicone, amodimethicone, sulfodimethicone, phosphodimethicone,borodimethicone, halodimethicone, fluorodimethicone, chlorodimethicone,bromodimethicone, charged dimethicone, and a combination thereof.

In certain embodiments, the composition further comprises one or moreadditional agents. In certain embodiments, the first part and/or thesecond part further independently comprise(s) one or more additionalagents, including cosmetic agents, therapeutic agents,stimuli-responsive agents, sensing agents, drug-delivery agents, opticalagents, coloring agents, pigments, scattering agents, sorbing agents,temperature-active agents, heat-active agents, UV-active agents,light-active agents, sound-active agents, pressure-active agents,motion-active agents, radiaoactive agents, electrical agents, magneticagents, and other beneficial agents.

Suitable cosmetic agents include, but are not limited to, moisturizers,sunscreens, UV protecting agents, skin-protectant agents, skin-soothingagents, skin-lightening agents, skin-brightening agents, skin-softeningagents, skin-smoothening agents, skin-bleaching agents, skin-exfoliatingagents, skin-tightening agents, cosmeceutical agents, vitamins,anti-oxidants, cell-signaling agents, cell-modulating agents,cell-interacting agents, skin tanning agents, anti-aging agents,anti-wrinkle agents, spot reducers, alpha-hydroxy acids, beta-hydroxyacids, ceramides, and a combination thereof.

Suitable therapeutic agents include, but are not limited to,pain-relievers, analgesics, anti-itching agents, anti-acne agents(beta-hydroxy acids, salicylic acid, benzoyl peroxide), anti-flammatoryagents, antihistamines, corticosteroids, NSAIDs (Non-SteroidalAnti-Inflammatory Drugs), anti-septic agents, antibiotics, anti-bacteriaagents, anti-fungal agents, anti-viral agents, anti-allergenic agents,anti-irritants, insect-repelling agents, phototherapy agents,blood-coagulating agents, antineoplastics, immune system boostingagents, immune system suppressing agents, coal tar, anthralin,fluocinonide, methotrexate, cyclosporine, pimecrolimus, tacrolimus,azathioprine, fluoruracil, ceramides, counterirritants, skin coolingcompounds, and a combination thereof.

Suitable beneficial agents include, but are not limited to,anti-oxidants, vitamins, vitamin D₃ analogues, retinoids, minerals,mineral oil, petroleum jelly, fatty acids, plant extracts, polypeptides,antibodies, proteins, sugars, humectants, emollients, a combinationthereof, and other similar agents beneficial for topical applicationknown in the art.

Another aspect of the present invention is directed to a compositionthat forms a layer on the skin, wherein the composition has a glasstransition temperature about or below body temperature. The term “glasstransition temperature” refers to the temperature at a transition fromthe solid state to the liquid state occurs. A glass transitiontemperature may be reported as a temperature (° C., ° F. or K). Glasstransition temperature can be measured in vitro, for example, usingthermal analysis instruments such as a Differential Scanning Calorimeter(DSC) or a Thermogravimetric Analysis (TGA). In certain embodiments, thecomposition that forms the layer has a glass transition temperaturebelow about 37° C. In preferred embodiments, the composition that formsthe layer has a glass transition temperature below about 25° C. Infurther preferred embodiments, the composition that forms the layer hasa glass transition temperature below about 0° C. In certain embodiments,the first part of the composition that forms the layer has a glasstransition temperature below about 37° C. In preferred embodiments, thefirst part of the composition that forms the layer has a glasstransition temperature below about 25° C. In further preferredembodiments, the first part of the composition that forms the layer hasa glass transition temperature below about 0° C. In certain embodiments,the second part of the composition that forms the layer has a glasstransition temperature below about 37° C. In preferred embodiments, thesecond part of the composition that forms the layer has a glasstransition temperature below about 25° C. In further preferredembodiments, the second part of the composition that forms the layer hasa glass transition temperature below about 0° C.

One aspect of the invention is directed to compositions that form alayer on a surface such as leather, glass, plastic, metal, ceramic,semiconductor, insulator, conductor, or the skin or the mucous membraneor the lip or the hair or the nail in-situ, i.e., in the location wherethe compositions disclosed herein are applied. The layer is preferablyformed without the need of heating or UV or light or electrical ormagnetic or pressure or sound exposure. The layer can be additionallyformed with exposure to one or more of heating, UV, light, electricity,magnetism, pressure and sound. Another aspect of the invention isdirected to compositions that form a layer on a surface such as leather,glass, plastic, ceramic, semiconductor, insulator, conductor, or metal,which is then applied over the skin or the mucous membrane or the lip orthe hair or the nail of a subject.

Another aspect of the present invention is directed to a compositionthat forms a layer that has low tackiness and forms quickly. The term“set-to-touch time” refers to the time when the layer has solidifiedsufficiently that it no longer flows and transfers to a finger or anartificial substrate that lightly touches it under normal force lessthan 50 Newtons. When the layer is “set-to-touch,” it becomessubstantially resistant to environmental factors, thus allowing the userto resume intended activities. The term “tack-free time” refers to thetime when the layer has solidified sufficiently that it no longer sticksto a finger or a substrate that lightly touches it under normal forceless than 0.15 Newtons, incurring stickiness to the film. When the layeris “tack-free,” it becomes substantially resistant to surface frictionand abrasion from environmental factors, thus allowing the user tofurther resume intended activities. Consequently, an appropriateset-to-touch time and tack-free time for the layer is important: alonger set-to-touch time and tack-free time would require the user towait a longer time before resuming activities, affecting consumercompliance; while a shorter set-to-touch time and tack-free time wouldrequire faster handling, application and/or spreading of thecomposition, which is not attainable by all users, or may otherwisenegatively affect the continuity, evenness, uniformity, and/or physicalproperties of the layer. We have discovered that increasing the molarratio of the low viscosity crosslinkable polymer(s), particularly lowviscosity alkenyl or alkynyl organopolymer in the composition (furtherparticularly in the second part in case of a two-part composition),reduced set-to-touch time and tack-free time of the layer formed. Thus,it is critical to have an appropriate amount of low viscositycrosslinkable polymer(s), particularly low viscosity alkenyl or alkynylorganopolymer in the composition to achieve a desirable set-to-touchtime and tack-free time.

In certain embodiments, the composition further comprises between 0.05%and 30% by weight one or more polymers and/or non-polymers that affectsthe set-to-touch time of the composition. Such polymers may be, but arenot necessarily, any one of the Polymers A, B or C. Other suitablepolymers include, but are not limited to, polytetrafluoroethylene(PTFE), poly(methyl methacrylate) (PMMA), polyethylene (PE orpolyethene), polypropylene (PP or polypropene), polyvinylidene fluoride(PVDF), polyurethane, acrylate, polyester such as nylons, polyether,polycarbonate, polysulfone, polyphosphate, or a combination thereof.Suitable non-polymers include, but are not limited to, particles such ascarbon, silica, boron nitride, metal oxides (e.g., zinc oxide, titaniumdioxide) and salts such as carbonate salts (e.g., calcium, magnesium,sodium salts), sulfates, phosphates, borates, halogenated salts, or acombination thereof.

Set-to-touch time can be measured on test subjects, for example, usingthe Set-to-Touch Time and Tack-Free Time of Film Test described herein,as modified from ASTM D5895-03. Set-to-touch time can also be measuredin vitro, for example, using the Set-to-Touch Time Film Test describedherein, using suitable substrates, for example, polyurethane,polypropylene and/or Cowhide Tooling leather. In certain embodiments,the composition has a set-to-touch time of greater than about 1 secondand less than about 10 minutes. In preferred embodiments, thecomposition has a set-to-touch time of greater than about 30 seconds andless than about 4 minutes. In further preferred embodiments, thecomposition has a set-to-touch time of greater than about 30 seconds andless than about 2 minutes. In further preferred embodiments, thecomposition has a set-to-touch time of greater than about 1 minute andless than about 2 minutes. In other preferred embodiments, thecomposition has a set-to-touch time of about 2 minutes. Polyurethane andpolypropylene have surface conditions preferably used for themeasurement of set-to-touch time due to its smoothness, and low aspectratio and cure characters in-vitro that are similar to the curecharacters on skin in-vivo.

Tack-free time is measured on test subjects by using the Set-to-TouchTime and Tack-Free Time of Film Test described herein, as modified fromASTM D5895-03. Tack-free time can also be measured in vitro, by usingthe Set-to-Touch Time and Tack-Free Time of Film Test described hereinover suitable substrates, for example, polyurethane, polypropylene, andCowhide Tooling leather. In certain embodiments, the composition has atack-free time of greater than about 1 second and less than about 10minutes. In preferred embodiments, the composition has a tack-free timeof greater than about 30 seconds and less than about 4 minutes. Infurther preferred embodiments, the composition has a tack-free time ofgreater than about 30 seconds and less than about 2 minutes. In furtherpreferred embodiments, the composition has a tack-free time of greaterthan about 1 minute and less than about 2 minutes. In other preferredembodiments, the composition has a tack-free time of about 2 minutes.Polyurethane and polypropylene have surface conditions preferably usedfor the measurement of tack-free time due to their smooth surface withlow aspect ratio and cure characters in-vitro that are similar to thecure characters on skin in-vivo.

Another aspect of the invention is directed to a composition that formsa thin layer on the skin. Thickness of the layer affects both itsbreathability, invisibility, compressibility, and its skin occlusiveeffects. “Thickness” refers to the average thickness of the layerapplied to a surface. Thickness of the layer formed can be measured invitro, for example, on a cross-section of a layer using microscopehaving a stage or ocular micrometer. Thickness of the layer is measuredon a specimen formed from the composition in vitro by using the ASTMD3767 Rubber-Measurement of Dimensions using the Mitutoyo ThicknessGauge test, modified to be used on free-standing film or on a layer overa substrate such as polyurethane, polypropylene, and Cowhide Toolingleather at room temperature and about 50% relative humidity.Polyurethane and polypropylene have surface conditions that arepreferably used for the thickness measurement due to their smoothsurface with low aspect ratio, allowing the layer to be easily removedas a free-standing layer. Cowhide Tooling leather has the preferredwater absorption and grain surface conditions needed for the thicknessmeasurement. Cowhide Tooling leather is commonly vegetable tanned andabsorbs water readily and dries out quickly because the fiber structureis less compact than that of chrome tanned leather. Cowhide Toolingleather is “full grain,” meaning the hair has been removed and theoriginal grain remains. Thickness of the layer can also be measured on aspecimen formed from the composition in vitro, for example, using theASTM D-6132 Nondestructive Measurement of Dry Film Thickness of AppliedOrganic Coatings using the PosiTector Ultrasonic Coating ThicknessGauges test, modified to use polyurethane as substrate at roomtemperature and about 50% relative humidity.

The thickness measurement of the substrate is made before and afterapplying the composition, from which the difference in thickness beforeand after applying the composition indicates the layer thickness. Incertain embodiments, the average thickness of the layer is less thanabout 0.1 mm (100 microns). In preferred embodiments, the averagethickness of the layer is about 0.5 to about 100 microns, about 1 toabout 90 microns, about 10 to about 80 microns, about 30 to about 70microns, about 40 to about 60 microns. In further preferred embodiments,the average thickness of the layer is about 50 microns.

Another aspect of the invention is directed to a composition that formsa durable layer on the skin. The durability of the layer on the skin canbe determined, for example, using the Film Durability on Skin testdescribed herein. We have discovered that increasing the molar ratioand/or viscosity/molecular weight of the high viscosity crosslinkablepolymer, particularly high viscosity alkenyl or alkynyl organopolymer inthe composition (further particularly in the first part in case of atwo-part composition), enhances durability, including both physicalintegrity and adhesion, of the layer formed. We have discovered thatthere exists a range of the relative molar ratio between the unsaturatedcarbon groups in the alkenyl or alkynyl organopolymer(s) and the hydridegroups in the organopolymer(s) in the composition (further particularlyin the first part in case of a two-part composition),that furtherenhances durability, including both physical integrity and adhesion, ofthe layer formed. We have further discovered that while pre-forming thelayer provides a cohesive layer with good adhesion to the substrate,in-situ formation of the layer promotes better adhesion to the surface,providing further enhanced layer durability. Gradients in cross-linkingdensity created by catalyst migration in a two-part composition mayfurther enhance adhesion to the substrate and, consequently, furtherenhanced layer durability. The balance of different viscosities anddifferent types of crosslinkable polymers in the compositions affectsthe balance between set-to-touch time, tack-free time, and durability ofthe layer formed.

In certain embodiments, the layer remains substantially intact on theskin for about 24 hours or more with common, routine daily activitiesand/or with demanding activities. In preferred embodiments, the layerremains substantially intact on the skin for at least about 30 hours,about 36 hours, about 48 hours, about 60 hours, about 72 hours, about 84hours, or about 96 hours with common, routine daily activities and/orwith demanding activities. In other preferred embodiments, the layerremains substantially intact on the skin for at least about 120 hours,about 144 hours, or about 168 hours with common, routine dailyactivities and/or with demanding activities. “Remain substantiallyintact” means that the layer remains on at least about 50%, at leastabout 60%, at least about 70%, at least about 80%, at least about 90%,at least about 95% of the area of the skin to which it was originallyapplied, or at least about 50%, at least about 60%, at least about 70%,at least about 80%, at least about 90%, at least about 95% by weightremains on the skin.

In certain embodiments, the layer remains at least about 50% intact, atleast about 60% intact, at least about 70% intact by either area or byweight on the skin for about 24 hours or more with common, routine dailyactivities and/or with demanding activities. In preferred embodiments,the layer remains at least about 80% intact by either area or by weighton the skin for about 24 hours or more with common, routine dailyactivities and/or with demanding activities. In other preferredembodiments, the layer remains at least about 90% intact, or at leastabout 95% intact by either area or by weight on the skin for about 24hours or more with common, routine daily activities and/or withdemanding activities. In certain embodiments, the layer remains at leastabout 50% intact, at least about 60% intact, at least about 70% intactby either area or by weight on the skin for at least about 30 hours,about 36 hours, about 48 hours, about 60 hours, about 72 hours, about 84hours, about 96 hours, at least about 120 hours, about 144 hours, orabout 168 hours with common, routine daily activities and/or withdemanding activities. In preferred embodiments, the layer remains atleast about 80% intact by either area or by weight on the skin for atleast about 30 hours, about 36 hours, about 48 hours, about 60 hours,about 72 hours, about 84 hours, about 96 hours, at least about 120hours, about 144 hours, or about 168 hours with common, routine dailyactivities and/or with demanding activities. In other preferredembodiments, the layer remains at least about 90% intact, or at leastabout 95% intact by either area or by weight on the skin for at leastabout 30 hours, about 36 hours, about 48 hours, about 60 hours, about 72hours, about 84 hours, about 96 hours, at least about 120 hours, about144 hours, or about 168 hours with common, routine daily activitiesand/or with demanding activities.

Another aspect of the invention is directed to a composition that formsa layer on the skin that resists peeling. Resistance to peeling isdetermined by measuring adhesive force using the Peel Adhesion testdescribed herein. The term “adhesive force” refers to the force per unitlength required to separate the materials adhered to a standardsubstrate such as leather or polypropylene or polyurethane. In certainembodiments, the adhesive force of the layer on polypropylene substrateis greater than about 2 N/m. In preferred embodiment, the adhesive forceof the layer on polypropylene substrate is greater than about is greaterthan about 5 N/m. In further preferred embodiments, the adhesive forceof the layer on polypropylene substrate is greater than about 20 N/m, 40N/m, 60 N/m, 80 N/m, greater than about 100 N/m, or greater than about200 N/m.

Another aspect of the invention is directed to a composition that formsa layer that is resistant to environmental factors, such as exposure toheat, cold, wind, water, humidity, bodily fluids (e.g., blood,pus/liquor puris, urine, saliva, sputum, tears, semen, milk, or vaginalsecretion), sebum, saline, seawater, soapy water, detergent water, orchlorinated water. Such resistance to environmental factors isrepresented by the minimal weight increase upon exposures to theseenvironmental factors. The weight change of the layer is determined byusing the ASTM D2765-95 Determination of Gel Content and Swell Ratio ofCrosslinked Ethylene Plastics test using a weight scale. In certainembodiments, the weight of the layer increases by less than about 10%upon exposure to such environmental factors at about 1-hour time point(i.e., 1 hour after application of the composition disclosed herein),about 4-hour, about 6-hour, about 12-hour, about 24-hour, about 30-hour,about 36-hour, about 48-hour, or between 48 hours and one week timepoint. In preferred embodiments, the weight of the layer increases byless than about 5%, or less than about 1% upon exposure to suchenvironmental factors at about 1-hour, about 4-hour, about 6-hour, about12-hour, about 24-hour, about 30-hour, about 36-hour, about 48-hour, orbetween 48 hours and one week time point. In further preferredembodiments, the weight of the layer increases by less than about 0.5%upon exposure to such environmental factors at about 1-hour, about4-hour, about 6-hour, about 12-hour, about 24-hour, about 30-hour, about36-hour, about 48-hour, or between 48 hours and one week time point.

In certain embodiments, the weight of the layer increases by less thanabout 50% upon exposure to such environmental factors at about 1-hourtime point (i.e., 1 hour after application of the composition disclosedherein), about 4-hour, about 6-hour, about 12-hour, about 24-hour, about30-hour, about 36-hour, about 48-hour, or between 48-hour and one-weektime point. In preferred embodiments, the weight of the layer increasesby less than about 5%, or less than about 1% upon exposure to suchenvironmental factors at about 1-hour, about 4-hour, about 6-hour, about12-hour, about 24-hour, about 30-hour, about 36-hour, about 48-hour, orbetween 48-hour and one-week time point. In further preferredembodiments, the weight of the layer increases by less than about 0.5%upon exposure to such environmental factors at about 1-hour, about4-hour, about 6-hour, about 12-hour, about 24-hour, about 30-hour, about36-hour, about 48-hour, or between 48-hour and one-week time point.

Another aspect of the invention is directed to a composition that formsa layer that is flexible, stretchable, elastic and body-movementconforming. Such flexible, stretchable, elastic and body-movementconforming properties of the layer are represented by the tensilemodulus, shear modulus, cyclic tensile residual strain, cyclic tensilehysteresis loss energy, fracture strain, fracture stress, and fracturetoughness measurements, which can be tested in vitro on a specimenformed from the composition using the methods described herein. For alayer to have the appearance and durability of normal, healthy skin,these physical properties of the layer preferably fall within specificranges so that the layer will not break when being deformed by bodymovements and will return to essentially the same state when the bodyreturns to the original state.

The terms “tensile strength,” or “ultimate tensile strength,” or“fracture stress,” or “stress at break,” or “maximum tensile stress,” or“ultimate tensile stress,” or “fracture strength,” or “breakingstrength” refer to stress at which a specimen fails via fracture.Tensile strength can be measured on a specimen formed from thecomposition in vitro, for example, using the Cyclic and Extension PullTest as described herein. In certain embodiments, the tensile strengthof the layer is greater than about 0.05 MPa, or greater than 0.10 MPa,or greater than 0.20 MPa, or greater than about 0.5 MPa. In preferredembodiments, the tensile strength of the layer is greater than about 1.0MPa, or greater than about 2.0 MPa. In preferred embodiments, thetensile strength of the layer is less than about 5 MPa. In furtherpreferred embodiments, the tensile strength of the layer is about 3.0MPa.

The terms “fracture strain,” or “elongation at break,” or “stretchinessat break,” or “strain at break,” or “maximum elongation,” or “maximumstrain,” or “maximum stretchiness” or “extension at break” or “maximumextension” refer to strain at which a specimen fails via fracture.Fracture strain can be measured on a specimen formed from thecomposition in vitro, for example, using the Cyclic and Extension PullTest as described herein. In certain embodiments, the fracture strain ofthe layer is greater than about 25%, greater than 50%, greater thanabout 100%, greater than about 200%, or greater than about 400%. Infurther preferred embodiments, the fracture strain of the layer isgreater than about 600%, greater than about 800%, greater than about1000%, greater than about 1200, or greater than about 1500%.

The terms “tensile modulus,” or “Young's modulus,” or “modulus ofelasticity,” or “stiffness,” or “tensile stiffness,” or “elasticmodulus” refer to the force per unit area that is needed to stretch anddeform a material beyond the initial length. Tensile modulus is aninverse of compliance, relating to flexibility or deformability of amaterial beyond the initial length. Tensile modulus can be measured on aspecimen formed from the composition in vitro, for example, using theCyclic and Extension Pull Test as described herein. Tensile modulus canalso be measured using the ASTM D5083 Tensile Properties of ReinforcedThermosetting Plastics Using Straight-Sided Specimens standard test. Incertain embodiments, the tensile modulus of the layer is about 0.01 toabout 40 MPa. In preferred embodiments, the tensile modulus of the layeris about 0.05 to about 20 MPa, or about 0.1 to about 10 MPa, about 0.1to about 5 MPa, about 0.1 to about 1 MPa. In further preferredembodiments, the tensile modulus of the layer is about 0.25 to about0.75 MPa. In further preferred embodiments, the tensile modulus of thelayer is about 0.5 MPa.

The terms “shear modulus” or “modulus of rigidity” or “shear stiffness”refer to the force per unit area that is needed to shear and deform amaterial beyond the initial length. Shear modulus is be measured on aspecimen formed from the composition in vitro by using the ASTM D7175Determining the Rheological Properties of Asphalt Binder using a DynamicShear Rheometer. In certain embodiments, the shear modulus of the layeris about 0.005 to about 10 MPa. In preferred embodiments, the shearmodulus of the layer is about 0.05 to about 5 MPa, or about 0.1 to about1 MPa. In further preferred embodiments, the shear modulus of the layeris about 0.25 to about 0.75 MPa. In further preferred embodiments, theshear modulus of the layer is about 0.5 MPa.

The term “cyclic tensile residual strain” refers to tensile residualstrain after cyclic tensile deformation. The term “residual strain”refers to strain that remains in a material after the original cause ofstress has been removed. Residual strain may be reported as plasticstrain, inelastic strain, non-elastic strain, or viscoelastic strain.The cyclic tensile residual strain can be measured on a specimen formedfrom the composition in vitro, for example, using the Cyclic andExtension Pull Test as described herein. In certain embodiments, thecyclic tensile residual strain of the layer is less than about 10%. Inpreferred embodiments, the cyclic tensile residual strain of the layeris less than about 5% or less than about 2.5%. In further preferredembodiments, the cyclic tensile residual strain of the layer is lessthan about 1%. In other preferred embodiments, the cyclic tensileresidual strain of the layer is less than about 0.5%, less than about0.25%, or less than about 0.1%.

The terms “cyclic tensile hysteresis loss energy” or “cyclic hysteresisstrain energy” refer to the excess energy being dissipated as heat whenthe specimen is subjected to cyclic tensile deformation. Cyclic tensilehysteresis loss energy can be measured on a specimen formed from thecomposition in vitro, for example, using the Cyclic and Extension PullTest as described herein. In certain embodiments, the cyclic tensilehysteresis loss energy of the layer is less than about 1 kJ/m³. Inpreferred embodiments, the cyclic tensile hysteresis loss energy of thelayer is less than about 0.5 kJ/m³. In further preferred embodiments,the cyclic tensile hysteresis loss energy of the layer is less thanabout 0.2 kJ/m³.

The terms “fracture toughness,” or “toughness,” or “tensile toughness,”or “deformation energy,” or “failure energy,” or “fracture energy” referto the ability to absorb energy of mechanical deformation per unitvolume up to the point of failure. Fracture toughness can be measured ona specimen formed from the composition in vitro, for example, using theCyclic and Extension Pull Test as described herein. In certainembodiments, the fracture toughness of the layer is greater than about500 kJ/m³. In preferred embodiments, the fracture toughness of the layeris greater than about 5,000 kJ/m³. In further preferred embodiments, thefracture toughness of the layer is greater than about 10,000 kJ/m³, orgreater than about 50,000 kJ/m³.

Another aspect of the invention is directed to a composition that formsa layer that is permeable to oxygen and water vapor, as represented bythe oxygen permeability coefficient, water vapor permeabilitycoefficient, oxygen transmission rate, water vapor transmission rate,oxygen permeance and/or water vapor permeance, which are tested in vitrousing the methods described herein.

The term “oxygen transmission rate” or OTR refers to the permeation fluxof oxygen through a membrane with certain thickness. Oxygen transmissionrate can be measured on a specimen formed from the composition in vitro,for example, using the ASTM F2622 Oxygen Gas Transmission Rate ThroughPlastic Film and Sheeting Using Various Sensors test. In certainembodiments, the oxygen transmission rate of the layer is greater thanabout 5×10⁻⁹ cm³/(cm²·s). In preferred embodiments, the oxygentransmission rate of the layer is greater than about 5×10⁻⁷ cm³/(cm²·s).In further preferred embodiments, the oxygen transmission rate of thelayer is greater than about 5×10⁻⁵ cm³/(cm²·s). In other preferredembodiments, the oxygen transmission rate of the layer is greater thanabout 5×10⁻⁴ cm³/(cm²·s), greater than about 5×10⁻³ cm³/(cm²·s), greaterthan about 5×10⁻² cm³/(cm²·s), greater than about 0.5 cm³/(cm²·s). Inpreferred embodiments, the oxygen transmission rate of the layer is lessthan about 5 cm³/(cm²·s).

The term “oxygen permeance” refers to the permeation flux of oxygenthrough a membrane with certain thickness, per unit oxygen vaporpressure difference between the membrane (typically in cmHg). Oxygenpermeance can be measured on a specimen formed from the composition invitro, for example, using the ASTM F2622 Oxygen Gas Transmission RateThrough Plastic Film and Sheeting Using Various Sensors test. In certainembodiments, the oxygen permeance of the layer is greater than about5×10⁻¹¹ cm³/(cm²·s·cm Hg). In preferred embodiments, the oxygenpermeance of the layer is greater than about 5×10⁻⁹ cm³/(cm²·s·cm Hg),or greater than about 5×10⁻⁷ cm³/(cm²·s·cm Hg). In further preferredembodiments, the oxygen permeance of the layer is greater than about5×10⁻⁶ cm³/(cm²·s·cm Hg). In other preferred embodiments, the oxygenpermeance of the layer is greater than about 5×10⁻⁵ cm³/(cm²·s·cm Hg),greater than about 5×10⁻⁴ cm³/(cm²·s·cm Hg), greater than about 5×10⁻³cm³/(cm²·s·cm Hg), or greater than about 5×10⁻² cm³/(cm²·s·cm Hg). Inpreferred embodiments, the oxygen permeance of the layer is less thanabout 0.5 cm³/(cm²·s·cm Hg).

The terms “oxygen permeability coefficient” or “intrinsic oxygenpermeability” refer to a measure of how fast the oxygen can move througha membrane, which involves a successive process of oxygen sorption intoa membrane then followed by oxygen diffusion through the membrane.Oxygen permeability coefficient can be measured on a specimen formedfrom the composition in vitro, for example, using the ASTM F2622 OxygenGas Transmission Rate Through Plastic Film and Sheeting Using VariousSensors test. In certain embodiments, the oxygen permeabilitycoefficient of the layer is greater than about 5×10⁻⁴ Barrer. Inpreferred embodiments, the oxygen permeability coefficient of the layeris greater than about 5×10⁻² Barrer, greater than about 5 Barrer, orgreater than about 50 Barrer. In further preferred embodiments, theoxygen permeability coefficient of the layer is greater than about 500Barrer. In other preferred embodiments, the oxygen permeabilitycoefficient of the layer is greater than about 5,000 Barrer. Inpreferred embodiments, the oxygen permeability coefficient of the layeris less than about 20,000 Barrer.

The term “water vapor transmission rate” or WVTR refers to thepermeation flux of water vapor through a membrane with certainthickness. Water vapor transmission rate can be measured on a specimenformed from the composition in vitro, for example, using the ASTM F1249Water Vapor Transmission Rate Through Plastic Film and Sheeting Using aModulated Infrared Sensor test. In certain embodiments, the water vaportransmission rate of the layer is greater than about 1×10⁻⁹ cm³/(cm²·s)and less than about 1.5×10⁻¹ cm³/(cm²·s). In preferred embodiments, thewater vapor transmission rate of the layer is greater than about 1×10⁻⁸cm³/(cm²·s). In further preferred embodiments, the water vaportransmission rate of the layer is greater than about 1×10⁻⁷ cm³/(cm²·s).In other preferred embodiments, the water vapor transmission rate of thelayer is greater than about 1×10⁻⁶ cm³/(cm²·s), greater than about1×10⁻⁵ cm³/(cm²·s), or greater than about 1×10⁻⁴ cm³/(cm²·s). Inpreferred embodiments, the water vapor transmission rate of the layer isless than about 1.5×10⁻² cm³/(cm²·s).

The term “water vapor permeance” refers to the permeation flux of watervapor through a barrier with certain thickness, per unit water vaporpressure difference between one side and the other side of the barrier(typically in cmHg). Water vapor permeance can be measured on a specimenformed from the composition in vitro, for example, using the ASTM F1249Water Vapor Transmission Rate Through Plastic Film and Sheeting Using aModulated Infrared Sensor test. In certain embodiments, the water vaporpermeance of the layer is greater than about 1×10⁻¹¹ cm³/(cm²·s·cm Hg)and less than about 2×10⁻³ cm³/(cm²·s·cm Hg). In preferred embodiments,the water vapor permeance of the layer is greater than about 1×10⁻¹⁰cm³/(cm²·s·cm Hg), or greater than about 1×10⁻⁹ cm³/(cm²·s·cm Hg). Infurther preferred embodiments, the water vapor permeance of the layer isgreater than about 1×10⁻⁸ cm³/(cm²·s·cm Hg). In other preferredembodiments, the water vapor permeance of the layer is greater than1×10⁻⁷ cm³/(cm²·s·cm Hg), or greater than 1×10⁻⁶ cm³/(cm²·s19 cm Hg). Inpreferred embodiments, the water vapor permeance of the layer is lessthan about 2×10⁻² cm³/(cm²·s·cm Hg).

The terms “water vapor permeability coefficient” or “intrinsic watervapor permeability” refer to a measure of how fast water vapor can movethrough a barrier, which involves a successive process of water vaporsorption into a barrier, followed by water vapor diffusion through thebarrier. Water vapor permeability coefficient can be measured on aspecimen formed from the composition in vitro, for example, using theASTM F1249 Water Vapor Transmission Rate Through Plastic Film andSheeting Using a Modulated Infrared Sensor test. In certain embodiments,the water vapor permeability coefficient of the layer is greater thanabout 1×10⁻³ Barrer and less than about 1×10⁶ Barrer. In preferredembodiments, the water vapor permeability coefficient of the layer isgreater than about 0.01 Barrer, greater than about 0.1 Barrer, greaterthan about 1 Barrer, greater than about 10 Barrer, greater than about100 Barrer, or greater than about 1×10³ Barrer. In further preferredembodiments, the water vapor permeability coefficient of the layer isgreater than about 1×10⁴ Barrer and less than about 1×10⁵ Barrer.

Another aspect of the invention is directed to a composition that formsa layer over skin such that the transepidermal water loss of the areatreated with the composition is reduced or comparable to untreated skin.The term “transepidermal water loss” refers to the measurement of thequantity of water that passes from inside a body through the epidermallayer to the surrounding atmosphere via diffusion and evaporationprocesses. Transepidermal water loss is measured by using theTransepidermal Water Loss (TEWL) Measurement Test as described herein.Differences in TEWL measurements caused by age, race, gender, and/orarea of the skin of the subject tested are generally less than thestandard error in the TEWL measurements. TEWL measurements can be madeat any time on or after about 30 minutes time point, for example, atabout 1-hour, about 4-hour, about 6-hour, about 12-hour, about 24-hour,about 30-hour, about 36-hour, about 48-hour, or between 48 hours and oneweek time point. In certain embodiments, the transepidermal water lossafter application of the composition is less than about 40 g/(m²·hr). Inpreferred embodiments, the transepidermal water loss after applicationof the composition is less than about 20 g/(m²·hr). In further preferredembodiments, the transepidermal water loss after application of thecomposition is less than about 10 g/(m²·hr). In other preferredembodiments, the transepidermal water loss after application of thecomposition is less than about 5 g/(m²·hr), or less than about 1g/(m²·hr).

Another aspect of the invention is directed to a composition that formsa layer over skin such that the skin hydration of the area treated withthe composition is improved or comparable to untreated skin. The term“skin hydration” refers to the measure of water content of the skin,typically through a Corneometer which is based on capacitancemeasurement of a dielectric medium near skin surface. Skin hydrationmeasurements can be made at any time on or after about 30-minute timepoint, such as at about 1-hour, about 4-hour, about 6-hour, about12-hour, about 24-hour, about 30-hour, about 36-hour, about 48-hour, orbetween 48 hours and one week time point. Skin hydration can bemeasured, for example, using a Corneometer pursuant to the procedure asdescribed in H. Dobrev, “Use of Cutometer to assess epidermalhydration,” Skin Research and Technology 2000, 6(4):239-244. In certainembodiments, the skin hydration after application of the composition isgreater than about 20 arbitrary units (normalized hydration value) ofCorneometer. In preferred embodiments, the skin hydration afterapplication of the composition is greater than about 40 arbitrary unitsof Corneometer. In other preferred embodiments, the skin hydration afterapplication of the composition is greater than about 60 arbitrary unitsof Corneometer, or greater than about 80 arbitrary units of Corneometer.

Skin hydration can also be measured, for example, using the procedure asdescribed in Clarys et al., Hydration measurements of the stratumcorneum: comparison between the capacitance method (digital version ofthe Corneometer CM 825 (R)) and the impedance method (Skicon-200EX (R)),Skin Research and Technology 2011, 18(3):316-23. In certain embodiments,the skin hydration after application of the composition is greater thanabout 20 microSiemens. In preferred embodiments, the skin hydrationafter application of the composition is greater than about 50microSiemens. In other preferred embodiments, the skin hydration afterapplication of the composition is greater than about 100 microSiemens,or greater than about 200 microSiemens, or about 400 microSiemens.

Another aspect of the invention is directed to a composition that formsa layer on the skin that tightens the skin. The tightening effect whichis caused by increasing the skin tension is quantified from a specimenformed from the composition in vitro by using the with the in-vitro curltest as described herein. In certain embodiments, the tension isincreased by greater than 0.1 N/m. In preferred embodiments, the tensionis increased by greater than 0.2 N/m. In preferred embodiments, thetension is increased by greater than 0.5 N/m, by greater than 1.0 N/m,by greater than 2.0 N/m, by greater than 5.0 N/m, by greater than 10N/m, by greater than 20 N/m, by greater than 50 N/m, by greater than 100N/m, by greater than 500 N/m, or by greater than 1,000 N/m.

Another aspect of the invention is directed to a composition that formsa layer on the skin such that the surface contour of the skin can bemodulated. The “surface contour of the skin” is observed with Canfield3-D Imaging System or visually with the comparative photos before andafter the application of the test composition.

In preferred embodiments, the composition forms a layer that iscosmetically elegant and has the appearance of normal, healthy, andyouthful skin of the subject to which the composition or layer isapplied. Consequently, the layer may convey cosmetic and therapeuticbenefits that reduce the appearance of any signs of ageing which includeunder eye bags, laugh lines, crow feets, forehead lines and wrinkles.

Another aspect of the invention is directed to a composition that formsa layer on the skin such that retraction time of the area treated withthe composition is decreased comparing with untreated skin. The term“retraction time” refers to the time taken for the skin to return to itsoriginal state after initial deformation by the Suction Cup device. Skinretraction time can be measured, for example, using a cutometer/suctioncup pursuant to the procedure as described in H. Dobrev, “Use ofCutometer to assess epidermal hydration,” Skin Research and Technology2000, 6(4):239-244. Skin retraction time measurements can be made at anytime on or after about 30 minutes time point, such as at about 1-hour,about 4-hour, about 6-hour, about 12-hour, about 24-hour, about 30-hour,about 36-hour, about 48-hour, or between 48 hours and one week timepoint. In certain embodiments, the skin retraction time afterapplication of the composition is decreased by about 5% to about 75%. Inpreferred embodiments, the skin retraction time after application of thecomposition is decreased by greater than about 10%. In other preferredembodiments, the skin retraction time after application of thecomposition is decreased by greater than about 25%, or greater thanabout 50%.

Another aspect of the invention is directed to a composition that formsa layer that is cosmetically elegant and has the appearance of normal,healthy skin of the subject to which the composition or layer isapplied. Consequently, the layer may convey cosmetic and therapeuticbenefits by masking, concealing, covering, or reducing the appearance ofskin conditions, e.g., conditions of compromised skin barrier function,symptoms of skin conditions, e.g., conditions of compromised skinbarrier function, and/or skin imperfections such as hyperpigmentation,melisma, and vitiligo.

Another aspect of the invention is directed to a composition that formsa layer that is cosmetically elegant and has the novel appearance of theskin of the subject to which the composition or layer is applied.Consequently, the layer may convey cosmetic and therapeutic benefits byenhancing the appearance of skin which includes tattoo and make-up.

In preferred embodiments, the composition further comprises one or moreoptics modifiers. In other preferred embodiments, the first part and/orthe second part further independently comprise one or more opticsmodifiers or particles. Optics modifiers or particles introduce surfacesresponsive to optical or photonic interaction, e.g., roughness for lightscattering, thereby imparting desirable shine, glossy, glow, matteappearance beyond or comparable to that of normal, healthy skin,preferably avoiding a significantly more shiny and/or glossy appearancethan normal skin. Suitable optics modifiers or particles include, forexample, pigments, dyes, polymers such as nylon (e.g., nylon-6,nylon-10, nylon-12), silicone, acrylic, acrylates/carbamate or otherpolymer or copolymer beads or particles, polyethylene beads,polymethymethacrylate beads, polystyrene beads, polyurethane beads;inorganics such as silica (e.g., silica and DMPA/isophthalic acid/SMDIcopolymer, available as ChronoSphere® Opticals from Lonza Group), boronnitride, talc, mica, alumina, titania; metal such as silvernanoparticles; and silicone, acrylic, acrylates/carbamate or otherpolymer or copolymer beads or particles. In certain embodiments, theoptics modifiers or particles have an average particle diameter ofbetween about 1 μm and about 20 μm. In a preferred embodiment, theoptics modifiers or particles have an average particle diameter ofbetween about 0.1 μm and about 20 μm. In preferred embodiments, theoptics modifiers or particles have an average particle diameter of 2 μmto 15 μm, and further preferably 5 to 10 μm.

Another aspect of the invention is directed to a composition that formsa layer that does not significantly change the shine and/or gloss of thearea over which the composition is applied. Shine and/or gloss can bemeasured on a specimen formed from the composition in vitro, forexample, using a Glossmeter pursuant to the ASTM D523 Specular Glosstest, at 20°, 60°, and/or 85° measurement angels. The light andmeasurement angel can be selected based on the anticipated gloss range.For example, if the measurement made at 60° is greater than about 70gloss units (GU), the measurement angle should be changed to 20° tooptimize measurement accuracy. Conversely, if the measurement made at60° is less than about 10 GU, the measurement angle should be changed to85° to optimize measurement accuracy. 45° or 75° measurement angle mayalso be used depending on the gloss of the substrate used for the test.Various materials can be used as substrate to mimic normal, healthy skinfor the test, for example, Cowhide Tooling leather in natural color.Shine and/or gloss change is indicated by the percentage increase ordecrease of gloss units in a measurement area after the treatmentcomparing to before treatment. In certain embodiments, the shine and/orgloss change of the area treated with the composition is less than about20%. In preferred embodiments, the shine and/or gloss change of the areatreated with the composition is less than about 10%. In furtherpreferred embodiments, the shine and/or gloss change of the area treatedwith the composition is less than about 5%.

Another aspect of the invention is directed to a composition that formsa layer that is clear, transparent, and/or optically invisible. Anotheraspect of the invention is directed to a composition that forms a layerso that the area with the composition applied has minimal color changebefore and after the application, such as color L* scale change, colora* scale change, and/or color b* scale change. Color L* scale, color a*scale and color b* scale are the three L*a*b* color space specified bythe International Commission on Illumination. Color L* scale, color a*scale and color b* scale changes can be measured on a specimen formedfrom the composition in vitro, for example, using a Minolta Color Meterpursuant to the ASTM E313 Calculating Yellowness and Whiteness Indicesfrom Instrumentally Measured Color Coordinates. Various materials can beused as substrate to mimic normal, healthy skin for the test, forexample, Cowhide Tooling leather in natural color.

In certain embodiments, the color L* scale change of the area treatedwith the composition is less than about 2. In preferred embodiments, thecolor L* scale change of the area treated with the composition is lessthan about 1.5. In other preferred embodiments, the color L* scalechange of the area treated with the composition is less than about 1, orless than about 0.5. In certain embodiments, the color a* scale changeof the area treated with the composition is less than about 2. Inpreferred embodiments, the color a* scale change of the area treatedwith the composition is less than about 1.5. In other preferredembodiments, the color a* scale change of the area treated with thecomposition is less than about 1, or less than about 0.5. In certainembodiments, the color b* scale change of the area treated with thecomposition is less than about 2. In preferred embodiments, the color b*scale change of the area treated with the composition is less than about1.5. In other preferred embodiments, the color b* scale change of thearea treated with the composition is less than about 1, or less thanabout 0.5.

Another aspect of the invention is directed to a composition that formsa layer that is translucent or opaque. In certain embodiments, thecomposition further comprises one or more colorants, including, but notlimited to, pigments, dyes (including fluorescent dyes), FD&C colors,D&C colors, lake colors, other color-imparting compounds, and acombination thereof. Other suitable colorants are disclosed, forexample, in the CTFA Cosmetic Ingredient Handbook, 2nd ed. 1992. Inpreferred embodiments, the color of the layer substantially matches thecolor of normal, healthy skin of the subject. In other preferredembodiments, the layer further comprises various colorants,pearlescents, patterns, designs, or a combination thereof, thusconveying make up, cosmetic, aesthetic, and/or decorative benefits.

In certain embodiments, a finishing formulation may be applied with orover the layer during or after its formation to provide a desiredtactile sensation or aesthetic look. For example, the finishingformulation may provide a silky, soft and/or smooth tactile sensation ora dewy, fresh, matte, shiny or luminescent aesthetic look. In certainembodiments, the finishing formulation comprises one or more of oils,esters or ethers, feel modifiers, tack modifiers, spreadabilityenhancers, adhesion modifiers, emulsifiers, emollients, surfactants,thickeners, film formers, humectants, preservatives, cosmetic agents,and/or therapeutic agents.

In certain embodiments, the finishing formulation comprises opticsmodifiers or particles, colorants, pearlescents, patterns, and/ordesigns.

In certain embodiments, the finishing formulation may be in variousforms, for example, liquid, lotion, cream, ointment, serum, gel, spray,foam, mousse, spritz, powder, or other suitable forms.

Another aspect of the invention is directed to a kit for use inmodifying skin condition of a subject; in treatment of conditions ofcompromised skin barrier function. In certain embodiments, the kitcomprises (i) a composition disclosed herein, and (ii) instructions foruse.

In certain embodiments, the kit comprises (i) a first part disclosedherein, (ii) a second part disclosed herein, and (iii) instructions foruse. In preferred embodiments, the first part and the second part areprevented from coming into contact prior to use. In preferredembodiments, the first part and the second part are packaged in separatecontainers or compartments, and applied one at a time or mixed togetherprior to or upon use.

In certain embodiments, the kit further comprises a finishingformulation. In certain embodiments, the kit further comprises acleanser suitable for removing the layer from the skin, e.g., thecleansers disclosed in U.S. Pat. No. 8,691,202. In certain embodiments,the kit further comprises one or more brush(es), swab(s), and/ormirror(s).

Another aspect of the invention is directed to a device formed byapplication of any of the compositions disclosed herein. Another aspectof the invention is a prosthetic device, for example, a prosthetic skin,that modulates moisture retention, oxygen permeability and water vaporpermeability on the skin formed by application of any of the compositiondisclosed herein. Another aspect of the invention is a prostheticdevice, for example, a prosthetic skin, that modulates opticalappearance on the skin formed by application of any of the compositiondisclosed herein. Another aspect of the invention is a prostheticdevice, for example, a prosthetic skin, that modulates mechanicalresponses of the skin formed by application of any of the compositiondisclosed herein. Another aspect of the invention is a prostheticdevice, for example, a prosthetic skin, that modulates electricalresponses of the skin (for example by incorporating graphene or magneticparticles, preferably in Part 1) formed by application of any of thecomposition disclosed herein. Another aspect of the invention is aprosthetic device, for example, a prosthetic skin, that modulatesmagnetic responses of the skin formed by application of any of thecomposition disclosed herein. Another aspect of the invention is aprosthetic device, for example, a prosthetic skin, that modulatespressure responses of the skin formed by application of any of thecomposition disclosed herein. Another aspect of the invention is aprosthetic device, for example, a prosthetic skin, that modulates pHresponses of the skin formed by application of any of the compositiondisclosed herein. Another aspect of the invention is a prostheticdevice, for example, a prosthetic skin, that modulates temperatureresponses of the skin formed by application of any of the compositiondisclosed herein. Another aspect of the invention is a prostheticdevice, for example, a prosthetic skin, that modulates heat responses ofthe skin formed by application of any of the composition disclosedherein. Another aspect of the invention is a prosthetic device, forexample, a prosthetic skin, that modulates sound responses of the skinformed by application of any of the composition disclosed herein.

Another aspect of the invention is directed to a method for modifyingskin functions, by including delivering agents (therapeutics andcosmetics). Non-limiting examples of skin functions that may be modifiedare skin barrier function; skin pigmentation; skin appearance, includingbut not limited to wards, acne (sebacic gland), melasma, ventiligo,psoriasis; contact dermatitis or other dermatitis such as stasisdermatitis; and pruritus. Non-limiting examples of therapeutics that maybe included are anti-inflammatories, anticoagulants, antibiotics andantiseptics. Therapeutics and cosmetics are administered to a subject inneed thereof, by applying to the subject's skin or body a composition asdescribed herein.

Another aspect of the invention is directed to a method for treatingconditions of compromised skin barrier function, includingdermatological disorders, skin conditions, and wounds, in a subject inneed thereof, by applying to the subject's skin or body a composition asdescribed herein.

Another aspect of the invention is directed to a method for treatingsymptoms of conditions of compromised skin barrier function in a subjectin need thereof, comprising applying to the subject's skin or body acomposition as described herein, thereby treating one or more symptomsof a condition of compromised skin barrier function.

Another aspect of the invention is directed to a method for occludingskin of a subject in need thereof, comprising applying to the subject'sskin or body a composition as described herein, thereby occluding theskin. “Occluding skin” means forming a barrier semi-permeable orimpermeable to water vapor directly or indirectly over skin. In certainembodiments, the layer is semi-occlusive in that the composition forms alayer that is semi-permeable to water vapor. Alternatively, the layer isfully-occlusive in that the composition forms a layer that isimpermeable to water vapor.

In another aspect of the invention, the occlusion enhances the efficacyof a topical drug also administered to the patient's skin. In oneembodiment, the topical drug is a corticosteroid and the disease for thetreatment of which the corticosteroid is administered is eczema. In oneembodiment, occlusion restores the skin's barrier function. In oneembodiment, occlusion enhanced drug delivery.

Occlusive Therapy with semi-occlusive or fully-occlusive layer has beenwell-established, particularly for atopic dermatitis treatment (fordetailed reference: Misha M. Heller, Eric S. Lee, Faranak Kamangar,Wilson Liao and John Y. M Koo (2012). Occlusive Therapy in AtopicDermatitis, Atopic Dermatitis—Disease Etiology and Clinical Management,Dr. Jorge Esparza-Gordillo (Ed.), ISBN: 978-953-51-0110-9).

We have discovered that our layer can impart the benefit of occlusion tomodify and/or restore the barrier function of skin.

Another aspect of the invention is directed to a method for treating asubject for a condition of compromised skin barrier function, or totreat a symptom of such a condition, comprising applying to thesubject's skin or body a composition as described herein.

Another aspect of the invention is directed to a method for deliveringan agent to a subject to treat a condition of compromised skin barrierfunction, or to treat a symptom of such a condition, comprising applyingto the subject's skin or body a composition as described herein, therebydelivering the agent to the subject.

In one aspect, the present invention imparts its benefit by controllingthe rate of delivery of therapeutic agents into the skin, or bymodifying and/or enhancing the efficacy of therapy with respect to theadministered dosage of therapeutic agents over time.

Another aspect of the invention is directed to a method for deliveringto a subject a therapeutic agent to treat a condition of compromisedskin barrier function, or to treat a symptom of such a condition,comprising applying to the subject's skin or body a composition asdescribed herein.

In another aspect, the invention imparts its benefit by occlusion andenhancing (trans)dermal drug delivery, with or without the presence ofpermeation enhancers in the composition described herein. The benefit ofocclusion in enhancing (trans)dermal drug delivery modifies and/orenhances the efficacy of drugs with respect to potency and correspondingside-effects.

Another aspect of the invention is directed to a method to mask,conceal, or cover conditions of compromised skin barrier function,symptoms of compromised skin barrier function, and/or skinimperfections, comprising applying to the subject's skin or body acomposition as described herein, thereby masking, concealing, orcovering the area with the conditions of compromised skin barrierfunction, symptoms of compromised skin barrier function, and/or skinimperfections.

Another aspect of the invention is directed to a method for treatingconditions of compromised skin barrier function, symptoms of compromisedskin barrier function, and/or skin imperfections in conjunction withother treatment agent(s) (topical medication, cosmetics and/or personalcare products, in the form of ointment, cream, lotion, gel, spray, foam,mousse, or other suitable forms), wherein said other treatment agent(s)is applied to the skin are first, then the composition disclosed hereinis applied over such other treatment agent(s) to provide a durablebarrier for the other treatment agent(s).

In certain embodiments, the condition of compromised skin barrierfunction is a dermatological disorder selected from eczema, psoriasis,ichthyosis, rosacea, chronic dry skin, cutaneous lupus, lichen simplexchronicus, xeroderma, acne, disease-driven secondary dermatologicaldisorder, ulcer, and a combination thereof In preferred embodiments, thecondition of compromised skin barrier function is selected from eczema,psoriasis, ichthyosis, rosacea, and chronic dry skin.

Identification and/or pre-treatment of the area of skin function (e.g.,washing, shaving, or otherwise preparing the area for treatment) may beperformed. After the optional pre-treatment, the composition is appliedto the area in need of treatment to form the layer over the entire or aportion of the area in need of treatment, thereby treating theconditions of skin function. In certain embodiments wherein thecomposition is a two-part composition, the first part and the secondpart are applied either one at a time or in combination to form thelayer.

Another aspect of the invention is directed to a method of modifying thesurface of the skin. In some embodiments, the surface of the skin ismodified chemically by altering its surface pH. In some embodiments, theskin is modified by covering portions of its surface with melanin for UVprotection. In some embodiments, the skin is modified by coveringportions of its surface with silicone to reduce its friction. In someembodiments, the skin is modified physically, such that eye-bags and/orlaugh-lines are reduced. In some embodiments, skin is modified bycovering portions of its surface with pigments for cosmetic purposes. Insome embodiments, skin is modified by covering portions of its surfacewith soft-focus elements to modify the appearance of the skin. In someembodiments, skin is modified by covering portions of its surface withcomponents that allow for electrical responses, for example byincorporating graphene or magnetic particles, preferably in Part 1.

Physically such as eye-bag, Optically such as pigments and soft-focus.

Another aspect of the invention is directed to a method of modifyingskin tension. A change in skin tension may modify the skin's surfacecontour and/or the skin's recoil dynamic after stress response. Asindividuals age, they generally lose skin tension and the recoil dynamicresponse of the skin.

The amount of the composition applied is determined by the size andlocation of the area to be treated as well as the type of conditions ofskin function, e.g., compromised skin barrier function, to be treated.

The layer may remain over the area until the conditions of compromisedskin barrier function resolve, or improve, or maybe removed after anappropriate period of time as determined by a skilled practitioner(e.g., a medical practitioner such as a physician) or by the subject.The application can be repeated as many times as needed in order toachieve a desired result.

Physical properties of the compositions were measured using the methods(either standard or described herein) and devices set forth. Suchmethods and devices are merely exemplary, and other tests, methods,materials, and/or devices may be known or developed appropriate to testthe properties of the compositions disclosed.

Unless otherwise specified, all properties of compositions, layersand/or devices disclosed herein are measured at room temperature (about22-25° C.) and about 1 atmosphere air pressure.

Rheometer Viscosity Measurement Test

The following test method may be used to determine the dynamic viscosity(Pa·s) of fluid materials at 0.5 s⁻¹, using a Bohlin CVO100 Rheometer(Malvern Instruments) mounted with 20 mm Parallel plate geometry.Similar Rheometers can be used for viscosity measurements. For eachmaterial tested, at least 3 samples are measured, and average viscosityand standard deviation of the measurements are recorded.

About 1 g of each test sample is required. Visually inspect the sampleto ensure the sample appears uniform. Turn on the Bohlin Rheometer andthe temperature controller; start the Bohlin software and load theviscosity stability test template; install the geometry and zero theinstrument. Make sure that both the geometry and plate are clean, whichis critical for accurate test results. Place about 1 g of the testsample onto the bottom plate of the Rheometer in a mound centered belowthe geometry. Lower the geometry to the correct gap (about 250 μm).Clean any excess sample from the sides of the geometry using the flatend of a spatula. Start the test and allow the test to run tocompletion, then record the viscosity (Pa·s) data.

Film Durability on Skin Test

Application of Test Composition. Healthy subjects (at least 3) areselected irrespective of age, race or gender. Tests are conducted atroom temperature and about 50% relative humidity. Drawn 4×4 cm² squareoutlines on selected volar forearm areas using a standard template asguide. Using a balance, weigh out appropriate amounts (e.g., about 0.1 gto about 0.3 g) of the test composition (or about 0.1 g of the firstpart and about 0.15 g of the second part in cases of a two-partcomposition) onto weigh boats (in cases of a two-part composition, donot mix). Apply the test composition evenly over the 4×4 cm² squares onthe forearm using a fingertip, preferably wearing finger cot. Make surethat all areas of the squares are covered by the composition. In case ofa two-part composition, a clean fingertip or fresh finger cot should beused to spread the second part gently over the first part, covering theentire first part area.

Measurement. The composition is allowed to sit untouched over the areafor about 15 minutes. The subject is then allowed to resume dailyactivities. The subjects are permitted to conduct either only routinedaily activities, or routine daily activities with demanding activities,for example, exercising, swimming, steam room, sauna, and the like. Thetype and length of each demanding activity are recorded. The layersformed by the test composition are left on skin for about 24 hours ormore. At certain time points after application of the composition,durability of layers are assessed by measuring the percentage of thearea intact on the skin using an 8×8 square grid of 0.5×0.5 cm² each(total 64 squares). Any excess layer outside of the 4×4 cm² square areais not considered in the evaluation. Each square is only considered tobe durable if there is no visible imperfection, e.g., seams, flaking,cracking, and/or peeling, of the layer. Record the observations.

Set-to-Touch Time and Tack-Free Time of Film Test

This method was modified from ASTM D5895-03 Evaluating Drying or CuringDuring Film Formation of Organic Coatings Using Mechanical Recorders.The materials and application of test composition to the selectedsubjects are the same as described in the Film Durability on Skin Test.The test can also be conducted on other substrates instead of humanskin, for example, on Cowhide Tooling leather in natural color,polyurethane, or polypropylene substrates with comparable results. Foreach composition tested, at least 3 samples are tested, and averageset-to-touch time, average tack-free time and standard deviation of themeasurements are recorded.

Measurement. Start a timer when the test composition (or the second partin case of a two-part composition) is applied to the entire test area onthe forearm. Allow the composition to sit untouched over the area for acertain period of time, e.g., 30 seconds or one minute. At certain timepoints, touch one corner of the test area lightly using a fingertip, andvisually evaluate: first the presence or absence of any test compositionon the fingertip (Set-to-Touch Time); then the presence or absence ofany film surface being pulled up by the fingertip (Tack-Free Time ofFilm Test). Repeat the fingertip evaluation on untouched portions of thetest area at a certain time interval, e.g., every 15 seconds or 30seconds or one minute. The time at which no more test composition isobserved on the fingertip is reported as the “set-to-touch time” of thetest composition. The time at which no more film surface is pulled up bythe fingertip is reported as the “tack-free time” of the testcomposition.

Set-to-Touch Time and Tack-Free Time of Film Test in-vitro

This method was modified from ASTM D5895-03 Evaluating Drying or CuringDuring Film Formation of Organic Coatings Using Mechanical Recorders.The materials and application of test composition to the selectedsubstrates are described as follows: Place a 50-micron spacer (forexample, one layer of 3M Magic Scotch Tape) onto the substrate sheetsize 4.5″×1.5″, forming an opening rectangular of 3.75″×0.75″, exposingthe substrate surface. Apply test composition onto the substrate, thengliding the glass slide back and forth along the spacer edges to deposita smooth and uniform layer of test composition. The test can also beconducted on many substrates such as on Cowhide Tooling leather innatural color, polyurethane, or polypropylene substrates with comparableresults. For each composition tested, at least 3 samples are tested, andaverage set-to-touch time, average tack-free time and standard deviationof the measurements are recorded.

Measurement. Start a timer when the test composition (or the second partin case of a two-part composition) is applied to the entire test area onthe substrate. Allow the test composition to sit untouched over the areaat room temperature and ambient humidity for a certain period of time,e.g., 30 seconds or one minute. At certain time points, place a 1.5 cm×4cm polypropylene sheet on the surface of the test composition, thenplace a 15 g weight on top of polypropylene sheet. Wait for 2 seconds,before removing the weight and the polypropylene sheet from the surfaceof the test composition. Visually evaluate: first the presence orabsence of any test composition on the polypropylene sheet. Repeat thepolypropylene sheet evaluation on untouched portions of the test area ata certain time interval, e.g., every 15 seconds or 30 seconds or oneminute. The time at which no more test composition on the polypropylenesheet is observed is reported as the “set-to-touch time” of the testcomposition. After “set-to-touch time” is reported, transfer thespecimen to the 30-degree slope surface to evaluate the “tack-freetime”. Place the specimen 6 inches up along the slope surface away fromthe lowest point and secure the specimen on the slope surface. Drop a1/32″ diameter stainless steel ball onto the top part of the filmsurface from a distance an inch above the film surface. Observe themovement of the stainless steel ball on the film surface as the balltrying to roll down on its own gravity. Report “tack-free time” when theball is able to roll from the top to the bottom part of the film surfacecontinuously, without any interruption from the frictional film surfaceas the film becomes tack-free.

Peel Adhesion Test

This test method for adhesive force was developed in accordance withASTM C794 Adhesion-in-Peel of Elastomeric Joint Sealants. Instron 3342single column tension/compression testing system (Instron, Norwood,Mass.) with 100N load cell (Instron #2519-103) mounted with extensiongrip geometry may be used, with polypropylene sheet of 1/32″ thicknessas test substrate. Other similar equipment and other soft, flexible testsubstrates can also be used to measure the peeling force. The materialsand application of test composition to the selected substrates aredescribed as follows: Place a 50-micron spacer (for example, one layerof 3M Magic Scotch Tape) onto the substrate sheet size 4.5″×1.5″,forming an opening rectangular of 3.75″×0.75″, exposing the substratesurface. Apply test composition onto the substrate, then gliding theglass slide back and forth along the spacer edges to deposit a smoothand uniform layer of test composition. Allow the test composition to situntouched over the area at room temperature and ambient humidity for 3hours. Then, place a silicone adhesive tape (Mepitac) of 0.75″ width ontop of the film to fully cover the film surface on the polypropylenesubstrate, ready for measurement. For each material tested, at least 3samples are measured, and average peeling force and standard deviationof the measurements are recorded.

Measurement. Partially peel the silicone tape-covered test specimen atone end by hand to separate enough of the silicone tape-covered filmfrom the polypropylene substrate for effective grip by extension gripgeometry mounts of the instrument. Secure each peeling side in its owninstrument grip. Make sure the strips are clamped substantially parallelto the geometry. Perform the extension test at a rate of 1 mm/s untilthe two peeling strips separate completely from each other. Record thepeeling force vs. time data. The sample's average peeling force (N/m) iscalculated by averaging the instantaneous force (N) measured by theinstrument during the experiment normalized by the sample width (0.75″or 0.019 m).

Curl Test for Surface Tension of Curved Specimen

The deposition of the test article on substrate such as skin or elasticband or parafilm results in residual compressive stress within the filmdue to volume loss (strain), which in turn translate to the tensilestress on the underneath substrate. The combined result of the filmdeposited on substrate could be observed and quantified based on thelevel of surface curvature of the substrate after the deposition of thefilm.

To prepare the test article for curl test, first the test article wasdeposited onto either an elastic synthetic rubber sheet or a parafilmsubstrate as described earlier in the application of test composition tothe selected substrates. The materials and application of testcomposition to the selected substrates are described as follows: Place a50-micron spacer (for example, one layer of 3M Magic Scotch Tape) ontothe substrate sheet size 4.5″×1.5″, forming an opening rectangular of3.75″×0.75″, exposing the substrate surface. Apply test composition ontothe substrate, then gliding the glass slide back and forth along thespacer edges to deposit a smooth and uniform layer of test composition.Allow the test composition to sit untouched over the area at roomtemperature and ambient humidity for 24 hours.

Measurement. Use a Vernier Caliper to measure the end-to-end distance ofthe width side of the test specimen that is curved upward. Theend-to-end distance refers to the chord length, forming an incompleteupward circle where subsequent calculation of corresponding radius ofthe circle is computed. Report the radius value and its reciprocal asthe “curvature” value. Use the curvature value to calculate the surfacetension incurred on the substrate. In the case of originally curvedsurface with inherent surface tension such as skin, the change insurface tension incurred by the deposited top layer, will modify theinherent surface tension accordingly.

Cyclic and Extension Pull Test

These test methods for Cyclic Tensile Residual Strain (Instant ResidualStrain), Cyclic Tensile Hysteresis Loss Energy, Tensile (Young's)Modulus, Shear Modulus, Tensile Strength/Maximum Stress, FractureStrain, and Fracture Toughness was developed to be better suited for thespecimens disclosed herein in compliance with ASTM D638, ASTM D412, ASTMD1876 test guidelines. Instron 3342 single column tension/compressiontesting system (Instron, Norwood, Mass.) with 100N load cell (Instron#2519-103) mounted with extension grip geometry may be used. Othersimilar equipment can also be used to measure the properties testedherein. For each material tested, at least 3 samples are measured, andaverage results and standard deviation of the measurements are recorded.

About 10 g of the composition tested is needed for each sample. Thesamples are cast inside dumbbell shaped molds mounted on Teflon,consistent with the ASTM D638 guidelines. The dimensions of the “neck”of the mold are about 20 mm in length, about 5 mm in width and about 1.5mm in depth. The dimensions of the “handles/bell” of the mold are about20 mm in length, about 15 mm in width and about 1.5 mm in depth, whichprovides adequate area to insure secure slip-free grip during testing.Level the top surface of the filled mold with a smooth microscope slide.Ensure that the molds are filled without voids and the top surface issmooth. The casted samples are allowed to fully cure and dry for about20 to about 30 hours. The specimens formed are extracted from theirindividual molds by means of a spatula. Width and thickness of the“neck” of the finished specimens are measured with a caliper, recordedand input into the instrument. The Area of the “neck” portion of thespecimen is calculated by its width and thickness.

Layers formed by compositions disclosed herein can also be tested onceseparated from the substrates. Such a layer can be formed or trimmedinto a rectangular shape, and the Area of a cross-section of a layer canbe calculated by its width and thickness. In such as case, the ends ofthe rectangular specimen would be considered the “handle/bell” portionswhereas the middle of the rectangular specimen would be considered the“neck” portion.

Mechanical characterization of specimens is carried out on the Instron3342 (Instron, Norwood Mass.) equipped with 100N load-cell. Dumbbell orrectangular shaped specimens are mounted onto the instrument via Instron2710-101 grips on each end, which are modified to insure the specimensdo not slip or fail inside the grips during testing. The specimen ismounted onto the instrument such that all the rectangular “handle/bell”portions of the specimen and none of the “neck” of the specimen arefixed within the instrument grips. Make sure that the specimen ismounted substantially vertical in both vertical planes. The instrumentgrip distance is adjusted such that the sample is at neutral extensionas indicated by the instrument force being close to zero (±0.01 N).

Two types of tests are performed sequentially on each specimen, firstthe Cyclic Test followed by the Extension Pull Test. It is noted thatthe Cyclic Test has negligible effects on the result of the ExtensionPull Test on the same specimen. Each test is preprogrammed into theinstrument.

Cyclic Test: The Cyclic Test is designed to determine the elasticity ofthe tested materials by measuring Cyclic Tensile Residual Strain(Instant Residual Strain). Generally, the more elastic the material, thefaster it returns to its original shape after deformation. Lower CyclicTensile Residual Strain scores indicate better elasticity. For perfectlyelastic materials, the Cyclic Tensile Residual Strain and cycle testarea should approach zero.

The specimen is mounted onto the instrument as described above. Stretchthe specimen slightly at about 1 mm/s by raising the geometry until aforce of 0.06-0.08 N is registered by the instrument, record thestretched length of the “neck” portion of the specimen as the initialspecimen length. Cyclic extension is performed at about 1 mm/s to amaximum extension of 15% of initial specimen length. A total of 15 (andup to 100) cycles are executed and the stress strain data is recorded.

The Cyclic Tensile Modulus is calculated as the straight line slope ofthe stress-strain curve of first cycle between 1% and 4% strain. The Rsquared value of the linear fit should be above 0.99 or the test datashould be recorded as outlier and discarded. The Cyclic Tensile ResidualStrain is calculated for each cycle as the strain difference between theloading and unloading curves at half the maximum stress achieved duringthe first cycle. The Cyclic Tensile Residual Strain for the first cycleas well as the average Cyclic Tensile Residual Strain for the 2ndthrough 12th cycles are recorded. The area bound by the loading andunloading curves of each cycle is also calculated as Cyclic TensileHysteresis Loss Energy. Good agreement is observed between the CyclicTensile Residual Strain and the calculated cycle area.

The majority of the specimens formed by the compositions disclosedherein are sufficiently flexible and elastic such that the Cyclic Testcould be repeated on the same sample without a significant change incalculated properties, which suggests that this test did not result inlong lasting changes to the tested specimens.

Extension Pull Test: The Extension Pull Test was used to determine thestiffness and stretchiness/flexibility of a material by measuring theTensile/Young's Modulus and fracture strain, respectively.

The specimen is mounted onto the instrument as described above. Stretchthe specimen slightly at about 10 mm/s by raising the geometry until aforce of 0.01-0.02 N is registered by the instrument, record thestretched length of the “neck” portion of the specimen as “OriginalLength.” The extension Tensile/Young's Modulus is calculated as thestraight line slope of the stress-strain curve between 6% and 11%strain. The R squared value of the linear fit should be above 0.99 orthe Tensile/Young's Modulus is calculated from a more linear 5% strainrange on the stress strain curve.

The Shear Modulus is determined from the same strain range as theTensile/Young's Modulus. Shear Modulus is calculated as the slope of thebest line fit between recorded stress and α−1/α², where α is 1 plus theinstantaneous strain.

Stretch the specimen at about 10 mm/s until it is broken at one side orcompletely. Record the force applied at the time when the specimen isbroken as the “Maximum Tensile Force.” Record the length of the “neck”portion of the specimen when it is broken extended beyond the OriginalLength of the specimen as the “Maximum Elongation Length.” TensileStrength/Maximum Stress is calculated as the Maximum Tensile Force overthe Area of the “neck” portion of the specimen. Fracture Strain iscalculated as the Maximum Elongation Length as percentage of theOriginal Length.

Fracture Toughness (kJ/m³) is calculated as the area under thestress-strain curve in the Extension Pull Test. The Yield Strain isdetermined as the strain at which the measured stress differed by morethan 10% from the Neo-Hookean stress; the multiple of Shear Modulus and(α−1/α²).

Transepidermal Water Loss (TEWL) Measurement Test

Evaporative water loss measurements provide an instrumental assessmentof skin barrier function. Evaporimetry with TEWL Probe is fullydescribed in Grove et al., Comparative metrology of the evaporimeter andthe DermaLab® TEWL probe, Skin Res. & Tech. 1999, 5:1-8 and Grove etal., Computerized evaporimetry using the DermaLab® TEWL probe, Skin Res.& Tech. 1999, 5:9-13. The guidelines established for using the Servo MedEvaporimeter described by Pinnagoda (Pinnagoda et al., Guidelines fortransepidermal water loss (TEWL) measurement, Contact Dermatitis 1990,22:164-178) are appropriate for the DermaLab® TEWL Probe as well.

Evaporative water loss measurements can be made using a recentlycalibrated Servo Med Evaporimeter. Alternatively, these measurements canbe made using a recently calibrated cyberDERM RG1 Evaporimeter System(Broomall, Pa.) with TEWL Probes (manufactured by Cortex Technology ofHadsund, Denmark and available in the US through cyberDERM, Inc.Broomall, Pa.), or other similar equipment.

Both Evaporimeters are based on the vapor pressure gradient estimationmethod pioneered by Gert E. Nilsson (e.g., Nilsson, G. E., Measurementof water exchange through skin, Med Biol Eng Comput 1977, 15:209-218).There are slight dimensional differences and the sensor technology isgreatly improved in the DermaLab® TEWL Probe but the underlyingprinciples of the measurement remain the same. Both probes contain twosensors that measure the temperature and relative humidity at two fixedpoints along the axis normal to the skin surface. This arrangement issuch that the device can electronically derive a value that correspondsto evaporative water loss expressed in gm/(m²·hr). The EvaporimeterSystem extracts value of average evaporative water loss rate collectedover a twenty-second interval once steady state conditions had beenachieved.

Subjects are treated with test compositions on selected volar forearmtest areas as described in the Film Durability on Skin Test.Measurements are taken from each of the volar forearm sites prior totreatment and at various time points (for example, at about 1-hour,about 4-hour, about 6-hour, about 12-hour, about 24-hour, about 30-hour,about 36-hour, about 48-hour, or between 48 hours and one week timepoint) after application of the composition. Measurements are takenfollowing a minimum of 25 minutes acclimation period in a controlledenvironment with the relative humidity maintained at less than about 50%and temperature maintained at about 19-22° C. Duplicate water lossreadings are taken from each site. TEWL properties (g/(m²·hr)) arecalculated based on the data recorded by the instrument.

Optical Measurement Based on Color L*a*b*Test

This test uses a Minolta CR-400 Chroma meter in accordance with theinstructions by the manufacturer, which are generally known in the art.Triplicate measurements of L*(D65), a*(D65), and b*(D65) are thencollected at ≥6 different locations of the test articles.

Barrier Protection Test Based on Viral Penetration

Barrier protection test based on viral penetration is performed toevaluate the barrier performance of protective materials, which areintended to protect against blood borne pathogen hazards. Test articleswere conditioned for a minimum of 24 hours at 21±5° C. and 60±10%relative humidity (% RH) and then tested for viral penetraton using aϕX174 bacteriophage suspension. At the end of the test, the observedside of the test article was rinsed with a sterile medium and assayedfor the presence of ϕX174 bacteriophage. The viral penetration methodcomplies with ISO 16604. Triplicate readings are taken from each testarticle.

Barrier Protection Test Based on Chemical Protection Against NickelContact

Nickel can be detected at the ppm level with a simple spot testcontaining 1% dimethylglyoxime and 10% ammonium hydroxide solution,which turns pink upon contact with nickel. A 0.2 M solution of nickel(II) sulfate hexahydrate solution is added to a substrate, and both arecovered by the test article. The spot test solution is subsequentlyapplied on the test. A change of color to pink indicates that the nickelhas penetrated the test article and come in contact with the colorsolution, or vice versa. In contrast, absence of color change indicatesthat the test article is not penetrated and that its barrier function isintact.

Barrier Protection Test Based on Protection from Ultraviolet Radiation

The presence of the test article could help reduce the skin absorptionof ultraviolet light, particularly when the test article contains SPFactive ingredients such as titanium dioxide, zinc oxide, avobenzone,octinoxate, octocrylene, homosalate, or oxybenzone.

To prepare the test article for barrier protection against UV radiation,first the test article was deposited onto a blank Cellophane sheetsubstrate as described earlier in the application of test composition tothe selected substrates. Cellophane sheet size 12.78 cm(L)×8.55 cm(W) isemployed to match plateholder of UV-Vis Spectrophotometer. Measure UVabsorbance with UV-Vis Spectrophotometer from the wavelength 260 nm to400 nm with 1 nm scan interval. Report absorption data based on averagedvalue of at least 4 different spot locations.

EXAMPLES Example 1 Testing the Properties of the Compositions and theLayers Formed by the Compositions

TABLE 1 Exemplary Methods for Measurement of Physical PropertiesPHYSICAL PROPERTIES METHODS USED DEVICE USED Viscosity ASTM C1749Rheological Rotational Rheometer Properties of Hydraulic CementiousPaste Using a Rotational Rheometer Glass transition temperature ASTMD3418-03 Transition Differential Scanning Temperatures of Polymers ByDSC Calorimeter (DSC) Layer Thickness ASTM D3767 Rubber - MitutoyoThickness Measurement of Dimensions using Gauge Cowhide Tooling leatherWeight increase upon ASTM D2765-95 Determination of Mettler Toledo Weighexposure to environmental Gel Content and Swell Ratio of Scale factorsCrosslinked Ethylene Plastics Tack free time on skin Set-to-Touch Timeof Film on Skin Visual Examination Durability on skin Film Durability onSkin Visual Examination Adhesive force Peel Adhesion Test in accordancewith Instron (Adhesion) ASTM C794 Tension of curved specimen Curl testfor surface tension of curved Instron specimen Surface contour Vectoranalysis of surface Canfield 3D Imaging Optical Coherence TomographyTensile strength Cyclic and Extension Pull Test/ Instron (UniaxialFracture strain ASTM D5083 Tensile Properties of Tensile) Tensilemodulus Reinforced Thermosetting Plastics Fracture toughness UsingStraight-Sided Specimens Cyclic tensile residual strain Cyclic tensilehysteresis Shear modulus ASTM D4065, D4440, D5279 Dynamic MechanicalAnalysis (DMA) Rotational Rheometer Oxygen transmission rate ASTM F2622Oxygen Gas MOCON (OTR) Transmission Rate Through Plastic Oxygenpermeance Film and Sheeting Using Various Oxygen permeability Sensorscoefficient Water vapor transmission rate ASTM F1249 Water Vapor MOCON(WVTR) Transmission Rate Through Plastic Water vapor permeance Film andSheeting Using a Water vapor permeability Modulated Infrared Sensorcoefficient Transepidermal water loss Transepidermal Water Loss ServoMed (TEWL) Measurement Test Evaporimeter/ CyberDERM RG1 EvaporimeterSystem Barrier protection (Biological) ISO16604 Viral Penetration TestΦX Bacteriophage Suspension Barrier protection (Chemical) Nickel TestColor assay for nickel contact Barrier protection (Radiation) OpticalTransmission UV/Vis Spectrophotometer Skin hydration H. Dobrev, “Use ofCutometer to Corneometer assess epidermal hydration,” Skin Research andTechnology 2000, 6(4): 239-244 Skin hydration Clarys et al., HydrationConductance/ measurements of the stratum Impedance Meter for corneum:comparison between the skin surface capacitance method (digital versionof the Corneometer CM 825 (R)) and the impedance method (Skicon- 200EX(R)), Skin Research and Technology 2011, 18(3): 316-23 Skin retractiontime H. Dobrev, “Use of Cutometer to Cutometer/Suction assess epidermalhydration,” Skin Cup Research and Technology 2000, 6(4): 239-244 ColorL*; ASTM E313 Calculating Minolta Color Meter Color a*; Yellowness andWhiteness Indices Color b* from Instrumentally Measured ColorCoordinates

Example 2 First Part (Formula P1-001)

TABLE 2 Active Ingredients of Formula P1-001 Weight Percent Phase No.Component Description (Wt %) A 1 Andisil VS 10,000 10,000 cSt Vinyl70.46% dimethicone A 2 Andisil XL-17 50 cSt Hydrogen 17.53% dimethiconeA 3 Aerosil R812s Silica silylate (fumed silica) 12.01%

All compositions herein were mixed using Dual Asymmetric CentrifugalLaboratory Mixer System (Hauschild, Germany).

Components 1 and 2 were added to a container and mixed for 2 minutes at2000 rpm. Then, Component 3 was added to the mixture and mixed for 12minutes at 2000 rpm (with manual scraping of the walls of the containerat every 2 minute interval to ensure complete dispersion of Component3).

Example 3 First Part (Formula P1-002)

TABLE 3 Active Ingredients of Formula P1-002 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 70.46%dimethicone A 2 Andisil XL-17 50 cSt Hydrogen 17.53% dimethicone A 3Aerosil R812s Silica silylate (fumed silica) 12.01%

Formula P1-002 was prepared using the same method as Formula P1-001.

Example 4 First Part (Formula P1-003)

TABLE 4 Active Ingredients of Formula P1-003 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 3.01%dimethicone A 2 Andisil VS 10,000 10,000 cSt Vinyl 48.15% dimethicone A3 Andisil XL-17 50 cSt Hydrogen 25.20% dimethicone A 4 Aerosil R812sSilica silylate (fumed silica) 10.91% A 5 Silsoft ETS Ethyl Trisiloxane5.45% A 6 Jeechem BUGL Butylene Glycol 7.27%

Components 1-3 were added to a container and mixed for 2 minutes at 2000rpm. Component 4 was added to the mixture and mixed for 12 minutes at2000 rpm (with manual scraping of the walls of the container at every2-minute interval to ensure complete dispersion of Component 4).Component 5 was slowly added to the mixture and mixed for 5 minutes at500 rpm. Component 6 was slowly added to the mixture and mixed for 30minutes at 500 rpm.

Example 5 First Part (Formula P1-004)

TABLE 5 Active Ingredients of Formula P1-004 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 3.31%dimethicone A 2 Andisil VS 10,000 10,000 cSt Vinyl 52.97% dimethicone A3 Andisil XL-17 50 cSt Hydrogen 27.72% dimethicone A 4 Aerosil R812sSilica silylate (fumed silica) 7.00% A 5 Aerosil R8200 Silica silylate(fumed silica) 9.00%

Components 1-3 were added to a container and mixed for 2 minutes at 2000rpm. Component 4 was added to the mixture and mixed for 12 minutes at2000 rpm (with manual scraping of the walls of the container at every2-minute interval to ensure complete dispersion of Component 4).Component 5 was added to the mixture and mixed for 12 minutes at 2000rpm (with manual scraping of the walls of the container at every2-minute interval to ensure complete dispersion of Component 5).

Example 6 First Part (Formula P1-005)

TABLE 6 Active Ingredients of Formula P1-005 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 9.92%dimethicone A 2 Andisil VS 10,000 10,000 cSt Vinyl 42.40% dimethicone A3 Andisil XL-11 45 cSt Hydrogen 20.75% dimethicone A 4 Aerosil R8200Silica silylate (fumed silica) 26.93%

Components 1-3 were added to a container and mixed for 2 minutes at 2000rpm. Then, Component 4 was added to the mixture and mixed for 12 minutesat 2000 rpm (with manual scraping of the walls of the container at every2-minute interval to ensure complete dispersion of Component 4).

Example 7 First Part (Formula P1-006)

TABLE 7 Active Ingredients of Formula P1-006 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 12.19%dimethicone A 2 Andisil VS 10,000 10,000 cSt Vinyl 60.96% dimethicone A3 Andisil XL-11 45 cSt Hydrogen 14.85% dimethicone A 4 Aerosil R812sSilica silylate (fumed silica) 12.00%

Formula P1-006 was prepared using the same method as Formula P1-005.

Example 8 First Part (Formula P1-007)

TABLE 8 Active Ingredients of Formula P1-007 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 14.69%dimethicone A 2 Andisil VS 10,000 10,000 cSt Vinyl 58.78% dimethicone A3 Andisil XL-11 45 cSt Hydrogen 14.53% dimethicone A 4 Aerosil R812sSilica silylate (fumed silica) 12.00%

Formula P1-007 was prepared using the same method as Formula P1-005

Example 9 First Part (Formula P1-008)

TABLE 9 Active Ingredients of Formula P1-008 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 24.94%dimethicone A 2 Andisil VS 10,000 10,000 cSt Vinyl 49.88% dimethicone A3 Andisil XL-11 45 cSt Hydrogen 13.18% dimethicone A 4 Aerosil R812sSilica silylate (fumed silica) 12.00%

Formula P1-008 was prepared using the same method as Formula P1-005.

Example 10 First Part (Formula P1-009)

TABLE 10 Active Ingredients of Formula P1-009 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 36.98%dimethicone A 2 Andisil VS 10,000 10,000 cSt Vinyl 36.98% dimethicone A3 Andisil XL-11 45 cSt Hydrogen 11.05% dimethicone A 4 Aerosil R812sSilica silylate (fumed silica) 15.00%

Formula P1-009 was prepared using the same method as Formula P1-005.

Example 11 First Part (Formula P1-010)

TABLE 11 Active Ingredients of Formula P1-010 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 56.50%dimethicone A 2 Andisil XL-17 50 cSt Hydrogen 14.05% dimethicone A 3Aerosil R812s Silica silylate (fumed silica) 9.63% A 4 Silsoft ETS EthylTrisiloxane 19.81%

Components 1-3 were mixed to form Formula P1-002 as described. Then,Component 4 was slowly added to the mixture and mixed for 30 minutes at500 rpm.

Example 12 First Part (Formula P1-011)

TABLE 12 Active Ingredients of Formula P1-011 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 52.84%dimethicone A 2 Andisil XL-17 50 cSt Hydrogen 13.15% dimethicone A 3Aerosil R812s Silica silylate (fumed silica) 9.01% A 4 Xiameter PMX-Dimethicone and 25.00% 1184 Trisiloxane

Components 1-3 were mixed to form Formula P1-002 as described. Then,Component 4 was slowly added to the mixture and mixed for 30 minutes at500 rpm.

Example 13 First Part (Formula P1-012)

TABLE 13 Active Ingredients of Formula P1-012 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 52.84%dimethicone A 2 Andisil XL-17 50 cSt Hydrogen 13.15% dimethicone A 3Aerosil R812s Silica silylate (fumed silica) 9.00% A 4 Andisil VS 10,00010,000 cSt Vinyl 0.01% dimethicone A 5 Xiameter PMX- Dimethicone and25.00% 1184 Trisiloxane

Components 1-3 were mixed to form Formula P1-002 as described. Component4 was added to the mixture and mixed for 5 minutes at 500 rpm. Then,Component 5 was slowly added to the mixture and mixed for 30 minutes at500 rpm.

Example 14 First Part (Formula P1-013)

TABLE 14 Active Ingredients of Formula P1-013 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 70.46%dimethicone A 2 Andisil VS 10,000 10,000 cSt Vinyl 0.01% dimethicone A 3Andisil XL-17 50 cSt Hydrogen 17.53% dimethicone A 4 Aerosil R812sSilica silylate (fumed silica) 12.00%

Components 1, 2 and 3 were added to a container and mixed for 2 minutesat 2000 rpm. Then, Component 4 was added to the mixture and mixed for 12minutes at 2000 rpm (with manual scraping of the walls of the containerat every 2 minute interval to ensure complete dispersion of Component4).

Example 15 First Part (Formula P1-014)

TABLE 15 Active Ingredients of Formula P1-014 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 52.84%dimethicone A 2 Andisil VS 10,000 10,000 cSt Vinyl 0.01% dimethicone A 3Andisil XL-17 50 cSt Hydrogen 13.15% dimethicone A 4 Aerosil R812sSilica silylate (fumed silica) 9.00% A 5 Xiameter PMX- Dimethicone and25.00% 1184 Trisiloxane

Components 1-4 were mixed to form Formula P1-013 as described. Then,Component 5 was slowly added to the mixture and mixed for 30 minutes at500 rpm.

Example 16 First Part (Formula P1-015)

TABLE 16 Active Ingredients of Formula P1-015 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 45.80%dimethicone A 2 Andisil XL-17 50 cSt Hydrogen 11.39% dimethicone A 3Aerosil R812s Silica silylate (fumed silica) 7.81% A 4 Xiameter PMX-Dimethicone and 35.00% 1184 Trisiloxane

Components 1-3 were mixed to form Formula P1-002 as described. Then,Component 4 was slowly added to the mixture and mixed for 30 minutes at500 rpm. cl Example 7

First Part (Formula P1-016)

TABLE 17 Active Ingredients of Formula P1-016 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 45.80%dimethicone A 2 Andisil VS 10,000 10,000 cSt Vinyl 0.01% dimethicone A 3Andisil XL-17 50 cSt Hydrogen 11.39% dimethicone A 4 Aerosil R812sSilica silylate (fumed silica) 7.80% A 5 Xiameter PMX- Dimethicone and35.00% 1184 Trisiloxane

Components 1-4 were mixed to form Formula P1-013 as described. Component5 was slowly added to the mixture and mixed for 30 minutes at 500 rpm.

Example 18 First Part (Formula P1-017)

TABLE 18 Active Ingredients of Formula P1-017 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 45.80%dimethicone A 2 Andisil XL-1 500 cSt Hydrogen 11.40% dimethicone A 3Aerosil R812s Silica silylate (fumed 7.80% silica) A 4 Xiameter PMX-Dimethicone and 35.00% 1184 Trisiloxane

Components 1-3 were mixed to form a pre-mixture, before Component 4 wasslowly added to the pre-mixture and mixed for 30 minutes at 500 rpm.

Example 19 First Part (Formula P1-018)

TABLE 19 Active Ingredients of Formula P1-018 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 45.80%dimethicone A 2 Andisil XL-1B 500 cSt Hydrogen 11.40% dimethicone A 3Aerosil R812s Silica silylate (fumed 7.80% silica) A 4 Xiameter PMX-Dimethicone and 35.00% 1184 Trisiloxane

Components 1-3 were mixed to form a pre-mixture, before Component 4 wasslowly added to the pre-mixture and mixed for 30 minutes at 500 rpm.

Example 20 First Part (Formula P1-019)

TABLE 20 Active Ingredients of Formula P1-019 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 45.80%dimethicone A 2 Andisil XL-17 50 cSt Hydrogen 11.40% dimethicone A 3Aerosil R812s Silica silylate (fumed 7.80% silica) A 4 Xiameter PMX-Dimethicone and 35.00% 1184 Trisiloxane

Components 1-3 were mixed to form a pre-mixture, before Component 4 wasslowly added to the pre-mixture and mixed for 30 minutes at 500 rpm.

Example 21 First Part (Formula P1-020)

TABLE 21 Active Ingredients of Formula P1-020 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 45.80%dimethicone A 2 Andisil XL-15 40 cSt Hydrogen 11.40% dimethicone A 3Aerosil R812s Silica silylate (fumed 7.80% silica) A 4 Xiameter PMX-Dimethicone and 35.00% 1184 Trisiloxane

Components 1-3 were mixed to form a pre-mixture, before Component 4 wasslowly added to the pre-mixture and mixed for 30 minutes at 500 rpm.

Example 22 First Part (Formula P1-021)

TABLE 22 Active Ingredients of Formula P1-021 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 45.80%dimethicone A 2 Andisil XL-13 500 cSt Hydrogen 11.40% dimethicone A 3Aerosil R812s Silica silylate (fumed 7.80% silica) A 4 Xiameter PMX-Dimethicone and 35.00% 1184 Trisiloxane

Components 1-3 were mixed to form a pre-mixture, before Component 4 wasslowly added to the pre-mixture and mixed for 30 minutes at 500 rpm.

Example 23 First Part (Formula P1-022)

TABLE 23 Active Ingredients of Formula P1-022 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 45.80%dimethicone A 2 Andisil XL-11 50 cSt Hydrogen 11.40% dimethicone A 3Aerosil R812s Silica silylate (fumed 7.80% silica) A 4 Xiameter PMX-Dimethicone and 35.00% 1184 Trisiloxane

Components 1-3 were mixed to form a pre-mixture, before Component 4 wasslowly added to the pre-mixture and mixed for 30 minutes at 500 rpm.

Example 24 First Part (Formula P1-023)

TABLE 24 Active Ingredients of Formula P1-023 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 45.80%dimethicone A 2 Andisil XL-10 45 cSt Hydrogen 11.40% dimethicone A 3Aerosil R812s Silica silylate (fumed 7.80% silica) A 4 Xiameter PMX-Dimethicone and 35.00% 1184 Trisiloxane

Components 1-3 were mixed to form a pre-mixture, before Component 4 wasslowly added to the pre-mixture and mixed for 30 minutes at 500 rpm.

Example 25 First Part (Formula P1-024)

TABLE 25 Active Ingredients of Formula P1-024 Phase No. ComponentDescription Wt % A 1 Andisil VS 65,000 65,000 cSt Vinyl 38.50%dimethicone A 2 Andisil CE-4 4 cSt Hydrogen 19.64% dimethicone A 3Aerosil R812s Silica silylate (fumed 7.80% silica) A 4 Xiameter PMX-Dimethicone and 34.00% 1184 Trisiloxane

Components 1-3 were mixed to form a pre-mixture, before Component 4 wasslowly added to the pre-mixture and mixed for 30 minutes at 500 rpm.

Example 26 First Part (Formula P1-025)

TABLE 26 Active Ingredients of Formula P1-025 Phase No. ComponentDescription Wt % A 1 Andisil VS 65,000 65,000 cSt Vinyl 10.48%dimethicone A 2 Andisil CE-4 4 cSt Hydrogen 47.72% dimethicone A 3Aerosil R812s Silica silylate (fumed 7.80% silica) A 4 Xiameter PMX-Dimethicone and 34.00% 1184 Trisiloxane

Components 1-3 were mixed to form a pre-mixture, before Component 4 wasslowly added to the pre-mixture and mixed for 30 minutes at 500 rpm.

Example 27 First Part (Formula P1-026)

TABLE 27 Active Ingredients of Formula P1-026 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 22.80%dimethicone A 2 Andisil XL-17 50 cSt Hydrogen 5.70% dimethicone A 3Aerosil R812s Silica silylate (fumed 4.00% silica) A 4 Matlake TMOTitanium dioxide 5.00% A 5 Zano 10 Plus Zinc oxide 5.00% A 6 XiameterPMX- Dimethicone and 40.00% 1184 Trisiloxane

Components 1-5 were mixed to form a pre-mixture, before Component 6 wasslowly added to the pre-mixture and mixed for 30 minutes at 500 rpm.

Example 28 First Part (Formula P1-027)

TABLE 28 Active Ingredients of Formula P1-027 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 41.22%dimethicone A 2 Andisil VS 10,000 10,000 cSt Vinyl 0.01% dimethicone A 3Andisil XL-17 50 cSt Hydrogen 10.25% dimethicone A 4 Aerosil R812sSilica silylate (fumed 7.02% silica) A 5 Xiameter PMX- Dimethicone and31.50% 1184 Trisiloxane A 6 Shin-Etsu KSG240 Dimethicone/PEG-10/15 3.50%Crosspolymer, Cyclopentasiloxane A 7 Dow Corning Bis-Isobutyl PEG/PPG-0.50% FZ2233 10/7/Dimethicone Copolymer B 8 PEG-200 Polyethylene glycol200 5.90% B 9 Triamcinolone Triamcinolone acetonide 0.10% acetonide

Components 1-4 were mixed to form Formula P1-013 as described. Component5-7 was slowly added to the mixture and mixed for 30 minutes at 500 rpm.The resultant Components 1-7 mixture is Phase A. In a separatecontainer, Components 7-12 were mixed for 10 minutes at 400 rpm. Theresultant Components 8-9 mixture is Phase B. Phase B was then slowlyadded to Phase A while mixing at 500 rpm, then stirred for 15 minutes at500 rpm. The resultant emulsion is then homogenized for 15 minutes at1150 rpm.

Example 29 First Part (Formula P1-028)

TABLE 29 Active Ingredients of Formula P1-028 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 43.97%dimethicone A 2 Andisil VS 10,000 10,000 cSt Vinyl 0.01% dimethicone A 3Andisil XL-17 50 cSt Hydrogen 10.93% dimethicone A 4 Aerosil R812sSilica silylate (fumed 4.49% silica) A 5 Xiameter PMX- Dimethicone and33.86% 1184 Trisiloxane A 6 Phoenix PS-112 Dimethicone PEG7 3.78%Phosphate A 7 Sensient Unicert CI 45410 pH-sensitive dye 0.20% RedK7053-J

Components 1-4 were mixed to form Formula P1-013 as described. Component5-7 was slowly added to the mixture and mixed for 30 minutes at 500 rpm.

Example 30 First Part (Formula P1-029)

TABLE 30 Active Ingredients of Formula P1-029 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 37.77%dimethicone A 2 Andisil VS 10,000 10,000 cSt Vinyl 0.01% dimethicone A 3Andisil XL-17 50 cSt Hydrogen 9.39% dimethicone A 4 Aerosil R812s Silicasilylate (fumed 6.43% silica) A 5 Xiameter PMX- Dimethicone and 28.86%1184 Trisiloxane A 6 Phoenix PS-112 Dimethicone PEG7 2.06% Phosphate A 7Celtig Cicarbo Graphene 15.46% Graphene Nanosheets

Components 1-4 were mixed to form Formula P1-013 as described. Component5-7 was slowly added to the mixture and mixed for 30 minutes at 500 rpm.

Example 31 First Part (Formula P1-030)

TABLE 31 Active Ingredients of Formula P1-030 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 0.68%dimethicone A 2 Andisil VS 10,000 10,000 cSt Vinyl 10.85% dimethicone A3 Andisil XL-11 45 cSt Hydrogen 2.55% dimethicone A 4 Aerosil R812sSilica silylate (fumed 1.92% silica) A 5 Xiameter PMX- Dimethicone and24.00% 1184 Trisiloxane A 6 Kobo TiO₂ white pigment 47.78% FAS70USI-E A7 Kobo FAS50EYSI- Fe₂O₃ yellow dispersion 9.62% E A 8 Kobo FAS55EYSI-Fe₂O₃ red dispersion 2.05% E A 9 Kobo FAS60EYSI- Fe₂O₃ black dispersion0.55% E

Components 1-4 were mixed to form Formula P1-013 as described. Component5-9 was slowly added to the mixture and mixed for 30 minutes at 500 rpm.

Example 32 First Part (Formula P1-031)

TABLE 32 Active Ingredients of Formula P1-031 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 1.19%dimethicone A 2 Andisil VS 10,000 10,000 cSt Vinyl 19.00% dimethicone A3 Andisil XL-11 45 cSt Hydrogen 4.45% dimethicone A 4 Aerosil R812sSilica silylate (fumed 3.36% silica) A 5 Xiameter PMX- Dimethicone and14.80% 1184 Trisiloxane A 6 Shin-Etsu KSG240 Dimethicone/PEG-10/15 4.25%Crosspolymer, Cyclopentasiloxane A 7 Dow Corning Bis-Isobutyl PEG/PPG-0.30% FZ2233 10/7/Dimethicone Copolymer A 8 Shin-Etsu KF6048 CetylPEG/PPG-10/1 0.50% Dimethicone B 9 water water 51.23% B 10 Jeecide CAP-4Phenoxyethanol, Caprylyl 0.33% Glycol B 11 Lubrizol PemulenAcrylates/C10-30 Alkyl 0.16% TR-2 Acrylate Crosspolymer B 12 LubrizolCarbopol Carbomer 0.48% Ultrez 10 Polymer B 13 Angus AMP-UltraAminomethyl propanol 0.09% PC 2000 (5% water)

Components 1-4 were mixed to form Formula P1-013 as described. Component5-8 was slowly added to the mixture and mixed for 30 minutes at 500 rpm.The resultant Components 1-8 mixture is Phase A. In a separatecontainer, Components 10-12 were gradually added to Component 9 thenmixed for 10 minutes at 400 rpm until the mixture is uniform. Then,dropwise add Component 13 then mixed for 10 minutes at 400rpm. Theresultant Components 9-13 mixture is Phase B. Phase B was then slowlyadded to Phase A while mixing at 500 rpm, then stirred for 15 minutes at500 rpm. The resultant emulsion is then homogenized for 15 minutes at1150 rpm.

Example 33 First Part (Formula P1-032)

TABLE 33 Active Ingredients of Formula P1-032 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 46.84%dimethicone A 2 Andisil XL-11 45 cSt Hydrogen 11.66% dimethicone A 3Aerosil R812s Silica silylate (fumed 6.50% silica) A 4 Xiameter PMX-1184Dimethicone and 35.00% Trisiloxane

Components 1-3 were mixed to form Formula P1-013 as described. Component4 was slowly added to the mixture and mixed for 30 minutes at 500 rpm.

Example 34 First Part (Formula P1-033)

TABLE 34 Active Ingredients of Formula P1-033 Phase No. ComponentDescription Wt % A 1 Andisil VS 165,000 165,000 cSt Vinyl 40.54%dimethicone A 2 Andisil XL-11 45 cSt Hydrogen 7.87% dimethicone A 3Aerosil R812s Silica silylate (fumed 6.60% silica) A 4 Xiameter PMX-Dimethicone and 44.99% 1184 Trisiloxane

Components 1-3 were mixed to form Formula P1-013 as described. Component4 was slowly added to the mixture and mixed for 30 minutes at 500 rpm.

Example 35 Second Part (Formula P2-001)

TABLE 35 Active Ingredients of Formula P2-001 Phase No. ComponentDescription Wt % A 1 Johnson Matthey Platinum Divinyldisiloxane, 99.00%C1142AF Divinyldisiloxane, Vinyl Dimethicone A 2 Andisil 2827-186LDivinyldisiloxane 1.00%

Component 2 was added to Component 1 and mixed for 15 minutes at 250rpm.

Example 36 Second Part (Formula P2-002)

TABLE 36 Active Ingredients of Formula P2-002 Phase No. ComponentDescription Wt % A 1 Shin-Etsu KF995 Cyclopentasiloxane 15.89% A 2 KoboNylon 10-I2 Nylon 12, Isopropyl 4.50% Titanium Triisostearate A 3 DowCorning Dimethicone Crosspolymer, 10.00% DC9045 ElastomerCyclopentasiloxane blend A 4 Shin-Etsu KSG240 Dimethicone/PEG-10/154.00% Crosspolymer, Cyclopentasiloxane A 5 Dow Corning Bis-IsobutylPEG/PPG- 0.10% FZ2233 10/7/Dimethicone Copolymer A 6 P2-001 PlatinumDivinyldisiloxane, 1.01% Divinyldisiloxane, Vinyl Dimethicone B 7 DIWater Water 29.50% B 8 Jeecide CAP-4 Phenoxyethanol, Caprylyl 0.50%Glycol B 9 Glycerin Glycerin 4.00% B 10 Propylene Glycol PropyleneGlycol 20.00% B 11 Butylene Glycol Butylene Glycol 10.00% B 12 SodiumChloride Sodium Chloride 0.50%

Component 2 was slowly added to Component 1 while mixing at 500 rpm,then stirred for 20 minutes at 500 rpm. Components 3-6 were mixed in aseparate container for 5 minutes at 500 rpm. The Components 1-2 mixturewas added to the container containing the Components 3-6 mixture, thenstirred for 10 minutes at 500 rpm. The resultant Components 1-6 mixtureis Phase A. In a separate container, Components 7-12 were mixed for 10minutes at 400 rpm. The resultant Components 7-12 mixture is Phase B.Phase B was then slowly added to Phase A while mixing at 500 rpm, thenstirred for 15 minutes at 500 rpm. The resultant emulsion is thenhomogenized for 15 minutes at 1150 rpm.

Example 37 Second Part (Formula P2-003)

TABLE 37 Active Ingredients of Formula P2-003 Phase No. ComponentDescription Wt % A 1 Shin-Etsu KF995 Cyclopentasiloxane 10.80% A 2 KoboNylon 10-I2 Nylon 12, Isopropyl 3.60% Titanium Triisostearate A 3 DowCorning Dimethicone Crosspolymer, 9.45% DC9045 Cyclopentasiloxane A 4Shin-Etsu KSG240 Dimethicone/PEG-10/15 3.60% Crosspolymer,Cyclopentasiloxane A 5 Dow Corning Bis-Isobutyl PEG/PPG- 0.45% FZ223310/7/Dimethicone Copolymer A 6 Andisil VS250 Vinyl Dimethicone 2.70% A 7Momentive Methylsilsesquioxane 10.00% Tospearl 3000A A 8 P2-001 PlatinumDivinyldisiloxane, 0.90% Divinyldisiloxane, Vinyl Dimethicone B 9 DIWater Water 22.05% B 10 Jeecide CAP-4 Phenoxyethanol, Caprylyl 0.45%Glycol B 11 Propylene Glycol Propylene Glycol 18.00% B 12 ButyleneGlycol Butylene Glycol 9.00% B 13 Baycusan C1008 Polyurethane 48, Water9.00%

Component 2 was slowly added to Component 1 while mixing at 500 rpm,then stirred for 20 minutes at 500 rpm. Components 3-6 were mixed in aseparate container for 5 minutes at 500 rpm. The Components 1-2 mixturewas added to the container containing the Components 3-6 mixture, thenstirred for 10 minutes at 500 rpm. Component 7 was slowly added to theComponents 1-6 mixture while mixing at 500 rpm, then stirred for 5minutes at 500 rpm. Component 8 was added to the Components 1-7 mixtureand stirred for 5 minutes at 500 rpm. The resultant Components 1-8mixture is Phase A. In a separate container, Components 9-13 were mixedfor 10 minutes at 400 rpm. The resultant Components 9-13 mixture isPhase B. Phase B was then slowly added to Phase A while mixing at 500rpm, then stirred for 15 minutes at 500 rpm. The resultant emulsion wasthen homogenized for 15 minutes at 1150 rpm.

Example 38 Second Part (Formula P2-004)

TABLE 38 Active Ingredients of Formula P2-004 Phase No. ComponentDescription Wt % A 1 Shin-Etsu KF995 Cyclopentasiloxane 11.39% A 2 KoboNylon Nylon 12, Isopropyl 3.80% 10-I2 Titanium Triisostearate A 3 DowCorning Dimethicone Crosspolymer, 9.975% DC9045 Cyclopentasiloxane A 4Shin-Etsu Dimethicone/PEG-10/15 3.80% KSG240 Crosspolymer,Cyclopentasiloxane A 5 Dow Corning Bis-Isobutyl PEG/PPG- 0.475% FZ223310/7/Dimethicone Copolymer A 6 Andisil VS250 Vinyl Dimethicone 2.85% A 7Momentive Methylsilsesquioxane 5.00% Tospearl 3000A A 8 P2-001 PlatinumDivinyldisiloxane, 0.96% Divinyldisiloxane, Vinyl Dimethicone B 9 DIWater Water 23.275% B 10 Jeecide CAP-4 Phenoxyethanol, Caprylyl 0.475%Glycol B 11 Propylene Glycol Propylene Glycol 19.00% B 12 ButyleneGlycol Butylene Glycol 9.50% B 13 Baycusan C1008 Polyurethane 48, Water9.50%

Formula P2-004 was prepared using the same method as Formula P2-003.

Example 39 Second Part (Formula P2-004)

TABLE 39 Active Ingredients of Formula P2-004 Phase No. ComponentDescription Wt % A 1 Dow Corning Dimethicone Crosspolymer, 41.18% DC9045Cyclopentasiloxane A 2 Shin-Etsu KSG240 Dimethicone/PEG-10/15 29.41%Crosspolymer, Cyclopentasiloxane A 3 Dow Corning Bis-Isobutyl PEG/PPG-5.88% FZ2233 10/7/Dimethicone Copolymer A 4 Andisil VS250 VinylDimethicone 17.65% A 5 P2-001 Platinum Divinyldisiloxane, 5.88%Divinyldisiloxane, Vinyl Dimethicone

Each component was added and mixed altogether for 15 minutes at 250 rpm.

Example 40 Second Part (Formula P2-005)

TABLE 40 Active Ingredients of Formula P2-005 Phase No. ComponentDescription Wt % A 1 Dow Corning Hexamethyldisoloxane 99.2% PMX-200Fluid, 0.65 CST A 2 P2-001 Platinum Divinyldisiloxane, 0.8%Divinyldisiloxane, Vinyl Dimethicone

Each component was added and mixed altogether for 5 minutes at 50 rpm.

Example 41 Second Part (Formula P2-006)

TABLE 41 Active Ingredients of Formula P2-006 Phase No. ComponentDescription Wt % A 1 Dow Corning Hexamethyldisoloxane 91.7% PMX-200Fluid, 0.65 CST A 2 Andisil 2827-186L 0.7 cSt Vinyl Dimethicone 7.5%(Divinyldisiloxane) A 3 P2-001 Platinum Divinyldisiloxane, 0.8%Divinyldisiloxane, Vinyl Dimethicone

Each component was added and mixed altogether for 5 minutes at 50 rpm.

Example 42 Second Part (Formula P2-007)

TABLE 42 Active Ingredients of Formula P2-007 Phase No. ComponentDescription Wt % A 1 Dow Corning Hexamethyldisoloxane 91.7% PMX-200Fluid, 0.65 CST A 2 Andisil VS6 6 cSt Vinyl Dimethicone 7.5% A 3 P2-001Platinum Divinyldisiloxane, 0.8% Divinyldisiloxane, Vinyl Dimethicone

Each component was added and mixed altogether for 5 minutes at 50 rpm.

Example 43 Second Part (Formula P2-008)

TABLE 43 Active Ingredients of Formula P2-008 Phase No. ComponentDescription Wt % A 1 Dow Corning Hexamethyldisoloxane 91.7% PMX-200Fluid, 0.65 CST A 2 Andisil VS20 20 cSt Vinyl Dimethicone 7.5% A 3P2-001 Platinum Divinyldisiloxane, 0.8% Divinyldisiloxane, VinylDimethicone

Each component was added and mixed altogether for 5 minutes at 50 rpm.

Example 44 Second Part (Formula P2-009)

TABLE 44 Active Ingredients of Formula P2-009 Phase No. ComponentDescription Wt % A 1 Dow Corning Hexamethyldisoloxane 91.7% PMX-200Fluid, 0.65 CST A 2 Andisil VS250 250 cSt Vinyl Dimethicone 7.5% A 3P2-001 Platinum Divinyldisiloxane, 0.8% Divinyldisiloxane, VinylDimethicone

Each component was added and mixed altogether for 5 minutes at 50 rpm.

Example 45 Second Part (Formula P2-010)

TABLE 45 Active Ingredients of Formula P2-010 Phase No. ComponentDescription Wt % A 1 Dow Corning Hexamethyldisoloxane 91.7% PMX-200Fluid, 0.65 CST A 2 Andisil VS500 500 cSt Vinyl Dimethicone 7.5% A 3P2-001 Platinum Divinyldisiloxane, 0.8% Divinyldisiloxane, VinylDimethicone

Each component was added and mixed altogether for 5 minutes at 50 rpm.

Example 46 Second Part (Formula P2-011)

TABLE 46 Active Ingredients of Formula P2-011 Phase No. ComponentDescription Wt % A 1 Dow Corning Hexamethyldisoloxane 91.7% PMX-200Fluid, 0.65 CST A 2 Andisil VS1000 1000 cSt Vinyl Dimethicone 7.5% A 3P2-001 Platinum Divinyldisiloxane, 0.8% Divinyldisiloxane, VinylDimethicone

Each component was added and mixed altogether for 5 minutes at 50 rpm.

Example 47 Second Part (Formula P2-012)

TABLE 47 Active Ingredients of Formula P2-012 Phase No. ComponentDescription Wt % A 1 Dow Corning Hexamethyldisoloxane 91.7% PMX-200Fluid, 0.65 CST A 2 Andisil VQM2050 1000 cSt Vinyl QM-resin 7.5% A 3P2-001 Platinum Divinyldisiloxane, 0.8% Divinyldisiloxane, VinylDimethicone

Each component was added and mixed altogether for 5 minutes at 50 rpm.

Example 48 Second Part (Formula P2-013)

TABLE 48 Active Ingredients of Formula P2-013 Phase No. ComponentDescription Wt % A 1 Dow Corning Hexamethyldisoloxane 95.7% PMX-200Fluid, 0.65 CST A 2 Andisil VS250 250 cSt Vinyl Dimethicone 2.5% A 3P2-001 Platinum Divinyldisiloxane, 0.8% Divinyldisiloxane, VinylDimethicone

Each component was added and mixed altogether for 5 minutes at 50 rpm.

Example 49 Second Part (Formula P2-014)

TABLE 49 Active Ingredients of Formula P2-014 Phase No. ComponentDescription Wt % A 1 Dow Corning Hexamethyldisoloxane 93.2% PMX-200Fluid, 0.65 CST A 2 Andisil VS250 250 cSt Vinyl Dimethicone 5.0% A 3P2-001 Platinum Divinyldisiloxane, 0.8% Divinyldisiloxane, VinylDimethicone

Each component was added and mixed altogether for 5 minutes at 50 rpm.

Example 50 Second Part (Formula P2-015)

TABLE 50 Active Ingredients of Formula P2-015 Phase No. ComponentDescription Wt % A 1 Dow Corning Hexamethyldisoloxane 89.2% PMX-200Fluid, 0.65 CST A 2 Andisil VS250 250 cSt Vinyl Dimethicone 10.0% A 3P2-001 Platinum Divinyldisiloxane, 0.8% Divinyldisiloxane, VinylDimethicone

Each component was added and mixed altogether for 5 minutes at 50 rpm.

Example 51 Second Part (Formula P2-016)

TABLE 51 Active Ingredients of Formula P2-016 Phase No. ComponentDescription Wt % A 1 Dow Corning Hexamethyldisoloxane 86.7% PMX-200Fluid, 0.65 CST A 2 Andisil VS250 250 cSt Vinyl Dimethicone 12.5% A 3P2-001 Platinum Divinyldisiloxane, 0.8% Divinyldisiloxane, VinylDimethicone

Each component was added and mixed altogether for 5 minutes at 50 rpm.

Example 52 Second Part (Formula P2-017)

TABLE 52 Active Ingredients of Formula P2-017 Phase No. ComponentDescription Wt % A 1 Dow Corning Hexamethyldisoloxane 89.0% PMX-200Fluid, 0.65 CST A 2 Andisil VS250 250 cSt Vinyl Dimethicone 10.0% A 3P2-001 Platinum Divinyldisiloxane, 1.0% Divinyldisiloxane, VinylDimethicone

Each component was added and mixed altogether for 5 minutes at 50 rpm.

Example 53 Second Part (Formula P2-018)

TABLE 53 Active Ingredients of Formula P2-018 Phase No. ComponentDescription Wt % A 1 Dow Corning Hexamethyldisoloxane 88.8% PMX-200Fluid, 0.65 CST A 2 Andisil VS250 250 cSt Vinyl Dimethicone 10.0% A 3P2-001 Platinum Divinyldisiloxane, 1.2% Divinyldisiloxane, VinylDimethicone

Each component was added and mixed altogether for 5 minutes at 50 rpm.

Example 54 Second Part (Formula P2-019)

TABLE 54 Active Ingredients of Formula P2-019 Phase No. ComponentDescription Wt % A 1 Dow Corning Hexamethyldisoloxane 88.6% PMX-200Fluid, 0.65 CST A 2 Andisil VS250 250 cSt Vinyl Dimethicone 10.0% A 3P2-001 Platinum Divinyldisiloxane, 1.4% Divinyldisiloxane, VinylDimethicone

Each component was added and mixed altogether for 5 minutes at 50 rpm.

Example 55 Second Part (Formula P2-020)

TABLE 55 Active Ingredients of Formula P2-020 Phase No. ComponentDescription Wt % A 1 Dow Corning Hexamethyldisoloxane 74.5% PMX-200Fluid, 0.65 CST A 2 Andisil VS250 250 cSt Vinyl Dimethicone 5.0% A 3P2-001 Platinum Divinyldisiloxane, 1.5% Divinyldisiloxane, VinylDimethicone A 4 Kobo Nylon 10-I2 Nylon 12, Isopropyl 4.0% TitaniumTriisostearate A 5 Momentive Methylsilsesquioxane 3.0% Tospearl 2000B A6 Propylene Glycol Propylene Glycol 10.0% A 7 Magnesium SulfateMagnesium Sulfate 2.0%

Each component was added and mixed altogether for 5 minutes at 50 rpm.

Example 56 Second Part (Formula P2-021)

TABLE 56 Active Ingredients of Formula P2-021 Phase No. ComponentDescription Wt % A 1 P2-001 Platinum Divinyldisiloxane, 1.08%Divinyldisiloxane, Vinyl Dimethicone A 2 Water water 48.96% A 3 EthanolEthyl alcohol 45.26% A 4 Baycusan C1008 Polyurethane 48, Water 4.17% A 5Lubrizol Carbopol Carbomer 0.49% Ultrez 10 Polymer A 6 Angus AMP-UltraAminomethyl propanol (5% 0.04% PC 2000 water)

Each component was added and mixed altogether for 5 minutes at 50 rpm.

Example 57 Second Part (Formula P2-022)

TABLE 57 Active Ingredients of Formula P2-022 Phase No. ComponentDescription Wt % A 1 Shin-Etsu KF995 Cyclopentasiloxane 10.83% A 2 KoboNylon Nylon 12, Isopropyl 3.80% 10-12 Titanium Triisostearate A 3 DowCorning Dimethicone Crosspolymer, 10.50% DC9045 Cyclopentasiloxane A 4Shin-Etsu Dimethicone/PEG-10/15 3.80% KSG240 Crosspolymer,Cyclopentasiloxane A 5 Dow Corning Bis-Isobutyl PEG/PPG- 0.475% FZ223310/7/Dimethicone Copolymer A 6 Andisil VS250 Vinyl Dimethicone 2.85% A 7Momentive Methylsilsesquioxane 5.00% Tospearl 3000A A 8 P2-001 PlatinumDivinyldisiloxane, 0.96% Divinyldisiloxane, Vinyl Dimethicone B 9 DIWater Water 23.275% B 10 Jeecide CAP-4 Phenoxyethanol, Caprylyl 0.475%Glycol B 11 Propylene Glycol Propylene Glycol 19.00% B 12 ButyleneGlycol Butylene Glycol 9.50% B 13 Baycusan C1008 Polyurethane 48, Water9.50%

Formula P2-004 was prepared using the same method as Formula P2-003.

Example 58 Second Part (Formula P2-023)

TABLE 58 Active Ingredients of Formula P2-023 Phase No. ComponentDescription Wt % A 1 Shin-Etsu KF995 Cyclopentasiloxane 11.75% A 2 KoboNylon Nylon 12, Isopropyl Titanium 4.00% 10-I2 Triisostearate A 3 DowCorning Dimethicone Crosspolymer, 10.50% DC9045 Cyclopentasiloxane A 4Shin-Etsu Dimethicone/PEG-10/15 4.00% KSG240 Crosspolymer,Cyclopentasiloxane A 5 Dow Corning Bis-Isobutyl PEG/PPG- 0.50% FZ223310/7/Dimethicone Copolymer A 6 Andisil VS250 Vinyl Dimethicone 3.00% A 7P2-001 Platinum Divinyldisiloxane, 1.25% Divinyldisiloxane, VinylDimethicone B 8 DI Water Water 33.80% B 9 Jeecide CAP-4 Phenoxyethanol,Caprylyl 0.50% Glycol B 10 Propylene Glycol Propylene Glycol 20.00% B 11Butylene Glycol Butylene Glycol 10.00% B 12 Sodium Chloride SodiumChloride 0.70%

Formula P2-004 was prepared using the same method as Formula P2-003.

Example 59 Comparison of Durability and Set-to-Touch Time of DifferentFormulations

TABLE 59 Durability and Set-to-Touch Time of Different FormulationsFirst part Set-to- VS165K* VS1OK† Silica‡ Second Dura- Touch Formula(wt%) (wt%) (wt%) part bility Time P1-001 0 70.46 12 P2-002 ~20 >15hours minutes P1-003 3.01 48.15 12.72 P2-002 <24 >10 hours minutesP1-004 3.31 52.97 16.0 P2-002 <24 >10 hours minutes P1-005 9.92 42.426.9 P2-002 <24 >10 hours minutes P1-006 12.19 60.96 12 P2-002 <24 >10hours minutes P1-007 14.69 58.78 12 P2-002 <24 >10 hours minutes P1-00824.94 49.88 12 P2-002 <24 >10 hours minutes P1-009 36.98 36.98 15 P2-002<24 >10 hours minutes P1-002 70.46 0 12 P2-002 30-48 >15 hours minutesP1-010 70.46 0 12 P2-003 24+ ~2 hours minutes P1-011 70.46 0 12 P2-00324+ ~2 hours minutes P1-012 70.46 0.01 12 P2-003 24+ ~2 hours minutesP1-014 70.46 0.01 12 P2-004 24+ ~2 hours minutes P1-015 70.46 0 12P2-004 24+ ~2 hours minutes Notes: *VS165K represents Andisil VS165,000, a high viscosity alkenyl organopolysiloxane; †VS1OK representsAndisil VS 10,000, a low viscosity alkenyl organopolysiloxane; ‡Silicarepresents Aerosil R812s, a fumed silica.

Example 60 Comparison of Durability of P1-016/P2-004 with a CommercialProduct

TABLE 60 Comparing Durability of P1-016/P2-004 with a Commercial Productat About 24 Hour Time Point Average Formula Durability STDEVP1-016/P2-004 92.45% 13.00% Commercial 38.45% 27.06% Product

Film Durability on Skin Tests were conducted comparing P1-016/P2-004 anda commercial product in accordance with Yu et al. (U.S. 20130078209),with four healthy subjects having the two formulas applied to skin areason opposite volar forearms. Durability was determined at about 24 hourtime points. Results are also shown in FIG. 1.

Example 61 Comparison of Set-to-Touch Time of P1-016/P2-004 with aCommercial Product

TABLE 61 Comparing Set-to-Touch Time of P1-016/P2- 004 with a CommercialProduct Average Set-to- Formula Touch Time STDEV P1-016/P2-004 2.33 mins0.82 mins Commercial 6.00 mins 1.73 mins Product

Set-to-Touch Time of Film Tests were conducted comparing P1-016/P2-004and a commercial product in accordance with Yu et al. (U.S.20130078209). Results are also shown in FIG. 2.

Example 62 Comparison of in-vivo Set-to-Touch Time and Tack-Free Time ofDifferent Formulations

TABLE 62 in-vivo Set-to-Touch Time and Tack-Free Time of DifferentFormulations Hydride:Vinyl mole ratio Low MW within the vinyl in Set-to-Tack-free First First Second Second touch time time Part Part Part part(seconds) (seconds) P1-017  6:1 P2-004 Yes >15 minutes > 15 minutesP1-018 11:1 P2-004 Yes 98 ± 15 seconds 240 ± 73 seconds P1-019 23:1P2-004 Yes 68 ± 15 seconds 150 ± 55 seconds P1-020 37:1 P2-004 Yes 60 ±0 seconds 60 ± 0 seconds P1-021 45:1 P2-004 Yes 15 ± 0 seconds 15 ± 0seconds P1-022 52:1 P2-004 Yes 15 ± 0 seconds 15 ± 0 seconds P1-023 90:1P2-004 Yes <15 seconds <15 seconds

Example 63 Comparison of in-vitro Set-to-Touch Time and Tack-Free Timeof Different Formulations

TABLE 63 in-vitro Set-to-Touch Time and Tack-Free Time of DifferentFormulations Hydride:Vinyl mole ratio Low MW within the vinyl in Set-to-Tack-free First First Second Second touch time time Part Part Part part(seconds) (seconds) P1-017  6:1 P2-004 Yes 860.00 ± 40.00 1020.00 ±30.00  P1-018 11:1 P2-004 Yes 286.67 ± 51.32 313.33 ± 56.86 P1-019 23:1P2-004 Yes 150.00 ± 10.00 190.00 ± 17.32 P1-020 37:1 P2-004 Yes 53.33 ±7.64  66.67 ± 11.55 P1-021 45:1 P2-004 Yes 51.67 ± 2.89 65.00 ± 8.66P1-022 52:1 P2-004 Yes 40.00 ± 0.00 50.00 ± 0.00 P1-023 90:1 P2-004 Yes33.33 ± 5.77  38.33 ± 10.41

Set-to-Touch Time and Tack-Free Time of Film Tests were conductedcomparing P1-017/P2-004 to P1-023/P2-004 ranking based on relativehydride-to-vinyl mole ratio within the first part. Results are alsoshown in FIG. 3.

Example 64 Comparison of In-Vivo Set-to-Touch Time and Tack-Free Time ofDifferent Formulations

TABLE 64 in-vivo Set-to-Touch Time and Tack- Free Time of DifferentFormulations Hydride:Vinyl Low MW mole ratio within vinyl in First theFirst Second Second Set-to- Part Part Part part touch time P1-023  1:1P2-002 No >15 mins P1-023  1:1 P2-004 Yes 10-15 mins P1-024 10:1 P2-002No 10-15 mins P1-024 10:1 P2-004 Yes 5-10 mins P1-016 20:1 P2-004 Yes <2mins

Example 65 Comparison of in-vitro Set-to-Touch Time and Tack-Free Timeof Different Formulations

TABLE 65 in-vitro Set-to-Touch Time and Tack-Free Time of DifferentFormulations Hydride:Vinyl mole ratio Low MW within the vinyl in Set-to-Tack-free First First Second Second touch time time Part Part Part part(mins) (mins) P1-016 20:1 P2-005 None >60 >60 P1-016 20:1 P2-006 7.5%0.7 cSt vinyl >60 >60 P1-016 20:1 P2-007 7.5% 6 cSt vinyl 20 21 P1-01620:1 P2-008 7.5% 20 cSt vinyl 2.5 3 P1-016 20:1 P2-009 7.5% 250 cStvinyl 2.5 5 P1-016 20:1 P2-010 7.5% 500 cSt vinyl 2.25 30 P1-016 20:1P2-011 7.5% 1000 cSt vinyl 2.25 >7 P1-016 20:1 P2-013 7.5% 500 cSt vinyl6 6 (Q-resin)

Set-to-Touch Time and Tack-Free Time of Film Tests were conductedcomparing P1-016/P2-005 to P1-016/P2-013 ranking based on relative vinylpolysiloxane viscosity which directly relate to molecular weight withinthe second part.

Example 66 Comparison of In-Vitro Set-to-Touch Time and Tack-Free Timeof Different Formulations

TABLE 66 in-vitro Set-to-Touch Time and Tack- Free Time of DifferentFormulations Hydride:Vinyl mole ratio 250 cSt within the vinyl wt %Set-to- Tack-free First First Second in Second touch time time Part PartPart part (mins) (mins) P1-016 20:1 P2-013 2.5% 2.5 >10 P1-016 20:1P2-014 5.0% 2.5 >5 P1-016 20:1 P2-009 7.5% 2.5 5 P1-016 20:1 P2-01510.0% 2.5 4 P1-016 20:1 P2-016 12.5% 2.5 2.5

Set-to-Touch Time and Tack-Free Time of Film Tests were conductedcomparing P1-016/P2-013 to P1-016/P2-016 ranking based on relativeweight percentage content of vinyl polysiloxane of 250 cSt viscosity inthe second part.

Example 67 Comparison of in-vitro Set-to-Touch Time and Tack-Free Timeof Different Formulations

TABLE 67 in-vitro Set-to-Touch Time and Tack- Free Time of DifferentFormulations Hydride:Vinyl mole ratio P2-001 within the wt % in Set-to-Tack-free First First Second Second touch time time Part Part Part part(mins) (mins) P1-016 20:1 P2-015 2.5% 2.5 4 P1-016 20:1 P2-017 5.0% 2.54 P1-016 20:1 P2-018 7.5% 2.5 4 P1-016 20:1 P2-019 10.0% 2.25 3

Set-to-Touch Time and Tack-Free Time of Film Tests were conductedcomparing P1-016/P2-017 to P1-016/P2-019 ranking based on relativeweight percentage content of P2-001 in the second part.

Example 68 Comparison of In-Vivo Durability of Different Formulationsafter 24 Hours

TABLE 86 Durability on Forearm Skin of Different Formulations after 24hours Hydride:Vinyl Low MW mole ratio vinyl in 24 hour First within theSecond Second durability Part First Part Part part (% intact) P1-017 6:1 P2-004 Yes 0% (no cohesive film formation) P1-018 11:1 P2-004 Yes87% ± 16% P1-019 23:1 P2-004 Yes 82% ± 11% P1-020 37:1 P2-004 Yes 70% ±22% P1-021 45:1 P2-004 Yes 60% ± 20% P1-022 52:1 P2-004 Yes 79% ± 12%P1-023 90:1 P2-004 Yes 22% ± 28%

Example 69 Comparison of In-Vitro Peeling Adhesion Test of DifferentFormulations

TABLE 69 in-vitro Peeling Adhesion Test of Different Formulations onPolypropylene Substrate Hydride:Vinyl Low MW Adhesion peel mole ratiovinyl in force per within the Second Second unit length First Part FirstPart Part part (N/m) P1-017  6:1 P2-004 Yes 8.64 ± 5.52 P1-018 11:1P2-004 Yes 12.67 ± 2.50  P1-019 23:1 P2-004 Yes 21.01 ± 4.55  P1-02037:1 P2-004 Yes 8.81 ± 2.66 P1-021 45:1 P2-004 Yes 17.25 ± 7.08  P1-02252:1 P2-004 Yes 15.70 ± 5.21  P1-023 90:1 P2-004 Yes 9.84 ± 3.16

In-vitro Peeling Adhesion Tests were conducted comparingP1-017/P2-004-P1023/P2-004 ranking based on relative hydride-to-vinylmole ratio within the first part. Results are also shown in FIG. 4.

Example 70 Demonstration of In-Vivo Film Resistance Against Rubbing

In-vivo film resistance against rubbing of the test compositionP1-030/P2-021 (full coverage colored film) and P1-028/P2-004(transparent colored film) on skin was demonstrated visually in FIG. 5.

Example 71 Clinical Evaluation of In-Vivo Durability after 6 Hours and24 Hours

Clinical Study (S16-01) was based on 25 healthy volunteers with normalskin. The test composition was self-applied under technicianinstructions on 4 test sites (forearm, inner elbow, leg, behind knee).Each test site covered the area of 4 cm×4 cm (˜0.1% BSA). Durability wasvisually evaluated after 6 hours and 24 hours by percentage of testcomposition area remaining after 24 hours and self-taken photographs at12 hours. In addition, durability was additionally evaluated with thedye exclusion on arm after 24 hours with photos, which also visuallyshowed film barrier properties. Results are also shown in FIG. 6.

Example 72 Comparison of In-Vitro Mechanical Properties of DifferentFormulations

In-vitro mechanical properties were conducted comparingP1-017/P2-004-P1023/P2-004 ranking based on relative hydride-to-vinylmole ratio within the first part.

TABLE 70 in-vitro Tensile Fracture Test for Mechanical Properties ofDifferent Formulations First Hydride: Vinyl mole Low MW ratio withinvinyl in Tensile Tensile Fracture Fracture the First Second SecondStrength Modulus Strain Toughness Part Part Part part (MPa) (MPa) (%)(MJ/m3) P1-017 6:1 P2-004 Yes did not cure into a cohesive test specimenafter 24 hours P1-018 11:1 P2-004 Yes 0.54 ± 0.15 0.34 ± 0.02 327.77 ±91.44% 1.02 ± 0.53 P1-019 23:1 P2-004 Yes 0.82 ± 0.24 0.34 ± 0.02 436.15 ± 110.54% 1.88 ± 0.87 P1-020 37:1 P2-004 Yes 0.78 ± 0.09 0.38 ±0.02 478.34 ± 52.57% 1.98 ± 0.39 P1-021 45:1 P2-004 Yes 0.88 ± 0.31 0.43± 0.02  406.32 ± 140.56% 2.03 ± 1.37 P1-022 52:1 P2-004 Yes 0.78 ± 0.120.35 ± 0.03 530.30 ± 54.97% 2.28 ± 0.60 P1-023 90:1 P2-004 Yes 0.88 ±0.19 0.63 ± 0.06 270.80 ± 43.89% 1.31 ± 0.44

TABLE 71 in-vitro Cyclic Tensile Test for Elasticity of DifferentFormulations Hydride:Vinyl Cyclic Tensile mole ratio Low MW Residualwithin the vinyl in Cyclic Tensile Hysteresis - First First SecondSecond Residual Strain Hysteresis Loss Part Part Part part (%) Energy(kJ/m³) P1-017  6:1 P2-004 Yes did not cure into a cohesive testspecimen after 24 hours P1-018 11:1 P2-004 Yes 1.32 ± 0.26% 0.383 ±0.071 P1-019 23:1 P2-004 Yes 0.92 ± 0.01% 0.280 ± 0.027 P1-020 37:1P2-004 Yes 0.91 ± 0.01% 0.327 ± 0.025 P1-021 45:1 P2-004 Yes 0.87 ±0.03% 0.353 ± 0.021 P1-022 52:1 P2-004 Yes 1.14 ± 0.01% 0.370 ± 0.027P1-023 90:1 P2-004 Yes 0.65 ± 0.12% 0.397 ± 0.111

Example 73 Comparison of In-Vitro Curl Test of Different Formulations

In-vitro Curl Test were conducted comparing P1-017/P2-004-P1023/P2-004ranking based on relative hydride-to-vinyl mole ratio within the firstpart.

TABLE 71 in-vitro Curl Test of Different Formulations Tensile Hydride:stress Vinyl on 500 mole Low microns ratio MW Chord skin within vinylLength / thickness, the in Curved Radius of 1M Pa skin First FirstSecond Second Length curvature modulus Part Part Part part (mm/mm) (mm)(kPa) P1-017 6:1 P2-004 Yes 0.93 ± 17.11 ± 14.61 ± 0.04 0.01 0.05 P1-01811:1 P2-004 Yes 0.69 ± 8.78 ± 26.21 ± 0.03 1.45 19.27 P1-019 23:1 P2-004Yes 0.99 ± 19.60 ± 12.76 ± 0.04 0.00 0.00 P1-020 37:1 P2-004 Yes 0.41 ±5.16 ± 75.88 ± 0.02 0.43 16.24 P1-021 45:1 P2-004 Yes 0.74 ± 11.06 ±22.60 ± 0.03 0.09 0.77 P1-022 52:1 P2-004 Yes 0.90 ± 16.21 ± 15.42 ±0.04 0.09 0.35 P1-023 90:1 P2-004 Yes 0.29 ± 3.65 ± 151.66 ± 0.01 0.064.22

Example 74 In-Vivo Optical Evaluation of Test Formulation on ForearmSkin

Test Materials L*(D65) a*(D65) b*(D65) 1 P1-016/P2-004 on skin#1 60.3811.72 15.74 2 P1-016/P2-004 on skin#2 59.56 11.09 15.35 3 P1-016/P2-004on skin#3 60.59 11.17 14.78 4 forearm skin#1 61.15 10.55 13.83 5 forearmskin#2 60.12 10.86 14.24 6 forearm skin#3 60.56 11.56 14.35 7 Tegaderm#165.96 7.23 14.83 8 Tegaderm#2 65.24 8.69 14.97 9 Tegarderm#3 66.37 6.9615.03

The optics was quantified using Minolta Color Meter from the volarforearm location for (i) control skin, (ii) P1-016/P2-004 on skin, (iii)3M Tegaderm™ wound dressing on skin. The evaluation of opticalinvisibility is based on grouping as of color L*a*b* scale distance fromthe control skin. Results are also shown in FIG. 7.

Example 75 In-Vitro Evaluation of Skin Surface Modulation

in-vivo evaluation of skin surface modulation was evaluated visually anddemonstrated in FIG. 8 on the modulation of facial contour near theunder eye areas as well as near the laugh line areas. The photos weretaken before, after 15 minutes and after 6 hours of the application ofthe test composition by P1-031/P2-022 (Right under eye & laugh line) andP1-032/P2-022 (Left under eye & laugh line) on female test subject (top)and by P1-033/P2-023 (Right under eye & laugh line) and P1-032/P2-023(Left under eye & laugh line) on male test subjects. All the testcomposition displayed the flattening appearance of the facial contour.

Example 76 In-Vitro Evaluation of Optical Modification of Skin

in-vivo evaluation of optical modification of skin was evaluatedvisually and demonstrated in FIG. 9 on the complete optical coverage ofnatural hyperpigmentation and on the complete coverage of tattoo. Thephotos were taken before and after the application of the testcomposition by P1-030/P2-021 on forearm skin of the subject.

Example 77 In-Vivo Demonstration of the Incorporation ofStimuli-Responsive Components into the Test Compositions for Enhancingthe Skin Function

Demonstration for enhancing the skin function via the incorporation ofstimuli-responsive components into the test compositions was shown inFIG. 10, which illustrates the incorporation of two differentstimuli-responsive components into the test composition on skin. (Left)P1-029/P2-004 with graphene, and (Right) P1-028/P2-004 with pH-sensitivedye.

Example 78 In-Vivo Barrier Evaluation Against Liquid Water Penetration

In-vivo barrier evaluation against liquid water penetration wereconducted through a demonstration of waterproof property of the testcomposition P1-016/P2-004, in comparison to petrolatum and control skin.First, a water-soluble dye was deposited on all three sites of the skinprior to the topical application of test compositions. After the topicalapplication of the test compositions, each skin site was then submersedinto a water bath, where the water-soluble dye at the control skin sitewas observed to wash away off the skin. Then, the remaining two siteswere washed with soap and hand-rubbed thoroughly, where thewater-soluble dye at the petrolatum site was also observed to wash awayoff the skin after rubbing. The only remaining site of the water-solubledye on skin was the skin site protected by test compositionP1-016/P2-004. The results were illustrated in FIG. 11.

Example 79 In-Vitro Barrier Evaluation Against Viral Penetration

TABLE 74 in-vitro barrier evaluation against viral penetrationPre-challenge Post-challenge Test article concentration concentrationAssay titer Visual Test number (PFU/mL) (PFU/mL) (PFU/mL) Penetrationresult P1-016/P2-004 4.2 × 10⁸ 4.9 × 10⁸ <1^(a) None seen Pass Negativecontrol 4.2 × 10⁸ 4.9 × 10⁸ <1^(a) None seen Acceptable Positive control4.2 × 10⁸ 4.9 × 10⁸ 9.3 × 10¹ Yes Acceptable ^(a)A value of <1 plaqueforming units (PFU/mL) is reported for assay plates showing no plaques.

Example 80 In-Vitro Barrier Evaluation Against Nickel Contact

In-vitro barrier evaluation against nickel contact were conductedcomparing P1-016/P2-004 (right side) against control (left side with notest composition). The control (left) displayed color change to pinkindicating a direct contact to nickel. The test composition containingP1-016/P2-004 (right) display no change in color indicating barrierprotection of the test article against chemicals such as nickel contact.Results are also shown in FIG. 12.

Example 81 In-Vitro Barrier Evaluation Against UV Radiation

In-vitro barrier evaluation against UV radiation were conductedcomparing P1-026/P2-004 against control blank and againstover-the-counter SPF 50 spray (Banana Boat). P1-026/P2-004 demonstratedbarrier protection against UV radiation, though not as good as SPF 50spray. Results are also shown in FIG. 13.

Example 82 In-Vitro Water Vapor Transmission Rate

Water vapor transmission test was done following the guidelines of ASTMD1653 on Standard Test Methods for Water Vapor Transmission of OrganicCoating Films, but under the condition of 10% RH at 37 C. The test is tocompare the level of moisture occlusive barrier by measuring how watervapor can transport through the films a reflected in the water loss fromthe reservoir inside the cup under the set condition of 10% RH at 37 C.Results are also shown in FIG. 14.

Example 83 In-Vitro Water Vapor Transmission Rate

TABLE 75 in-vitro water vapor transmission rate 15° C., 50% RH WaterVapor Transmission Water Vapor Rate Transmission Test Water Vapor (g/m2· day) Condition Transmission extrapolated to 50- Compar- SampleThickness Rate micron film ative Description (microns) (g/m2 · day)thickness Ratio Petrolatum 4,000 0.097 0.64  1x (control) P1-016/ 320107 28.53 45x P2-004

Example 84 In-Vitro Oxygen Transmission Rate

TABLE 76 in-vitro oxygen transmission rate 25 C., 0% RH, 760 mmHg, 100%O2 in carrier gas of 98% N2 and 2% H2 Oxygen Transmission Rate OxygenTransmission Oxygen (L/m2 · day) Test Condition Transmissionextrapolated to Compar- Sample Thickness Rate 50-micron film ativeDescription (microns) (cc/m2 · day) thickness Ratio Petrolatum 2,000 1000.167 1x   (control) P1-016/ 320 106,000 30.48 182.5x P2-004

Example 85 Clinical Evaluation of In-Vivo Transepidermal Water Loss(TEWL) after 2, 6, and 24 Hours by Evaporimeter Measurement

Clinical Study (S15-28) was based on 8 healthy volunteers with normalskin. The test composition was applied by technician on volar forearmsite with an arm guard worn for 6 hours. P1-016/P2-024 was compared withpetrolatum on two different test sites, normal skin versus damaged skin(dry shaved). Each test site covered the area of 4 cm×4 cm (˜0.1% BSA).TEWL was measured by Evaporimeter before the application of test articleand after 2, 6, and 24 hours. Prior to each TEWL measurement, subjectswere equilibrated for 45 minutes. Initial TEWL reports for all intactskin sites averaged at 4.85 g/m²/hr, as opposed to for all dry shavedskin sites averaged at 16.92 g/m²/hr. Results are shown in FIG. 15.

Example 86 Ex-Vivo Dermal Drug Delivery Via Franz Diffusion Cell

The ex-vivo study via Franz diffusion cell on cadaver skin was todetermine the rate and extent of skin permeation of a steroid drug“Triamcinolone Acetonide” from three different formulation combinationsinto and through intact human cadaver skin using a Franz diffusion cellsystem.

Test articles comprised of (1) commercial over-the-counter 0.1%Triamcinolone Acetonide lotion (TA) from Versa Pharma, (2) P1-016/P2-004layered on top of TA from Versa Pharma, and (3) P1-027/P2-004. Each ofthem contained 0.1% Triamcinolone Acetonide. Concentrations of theActive were measured in the receptor chamber of the diffusion cell atvarying time points. Upon conclusion of the diffusion study, the skinwas sequentially tape-stripped and split into epidermal and dermallayers. Triamcinolone acetonide concentration in each of the binnedtapestrips and epidermal and dermal tissues was extracted using anextraction solvent and was also analyzed with an Agilent G6120 HPLCsystem with a LC-MS detector.

Skin Preparation: Dermatomed intact human cadaver skin was purchasedfrom the New York Fire Fighter's Tissue Bank (NYFFTB). The donor ID#from the tissue bank was: AV011816 #5. The donor information supplied byNYFFTB was: race: Caucasian, sex: male, age: 47, donor site: posteriorleg. Upon receipt of the skin from the tissue banks, the skin was storedfrozen at −20° C. until the morning of the experiment. Prior to use, theskin was removed from the freezer and allowed to fully thaw at roomtemperature. Only areas of the skin that were visually intact were usedduring the experiment.

Receptor fluid preparation: Based on the results of solubility studies,a receptor fluid of phosphate buffered saline (PBS) at pH 7.4 with 2wt %hydroxypropyl-beta-cyclodextrin (HPBCD) was chosen. The solubility oftriamcinolone acetonide in this receptor fluid was measured to be ˜282μg/ml—which is sufficient to maintain sink conditions in the receptorfluid throughout the course of the flux study. The preparation anddegassing of the receptor fluid was was prepared at an appropriate pHand degassing was carried out by filtering the receptor fluid through aZapCap CR 0.2 μm membrane while pulling vacuum.

Diffusion cell assembly: Custom made Franz diffusion cells (FDCs) with areceptor volume of 3.3 ml were used for the experiment. The availablediffusional surface area of the skin for each cell is 0.55 cm². Thereceptor fluid was maintained at 32° C.±0.5° C. during the experimentusing a stirring dry block heater and the fluid was continuouslyagitated with a stir bar. The steps for assembling the diffusion cellsare outlined below:

-   -   The cadaver skin was removed from the freezer and allowed to        defrost in a bio-safety hood for 30 minutes. The skin was        thoroughly defrosted prior to opening the package.    -   The cadaver skin was removed from the package and placed on the        bio-safety hood countertop with the stratum corneum side up. The        skin was patted dry with a Kimwipe, then sprayed with fresh PBS        and patted dry again. This process was repeated 3 more times to        remove any residues present on the skin.    -   The receptor wells were then filled with the degassed receptor        fluid. A Teflon coated stir bar was added to each receptor well.    -   The defrosted cadaver skin was examined and only areas with even        thickness and no visible damage to the surface were used.    -   The skin was cut into ˜2 cm×2 cm squares.    -   The skin piece was centered on the donor cells, stratum corneum        (SC) side up.    -   The skin was centered again and the edges flattened out. The        donor and receptor cells were then aligned and clamped together        with a pinch clamp.    -   Additional receptor fluid was added where necessary. Any air        bubbles present were removed by tilting the cell, allowing air        to escape along the sample port.    -   Diffusion cells were then placed in the stirring dry block        heaters and allowed to rehydrate for 20 minutes from the        receptor fluid. The block heaters were maintained at 32°        C.±0.5° C. throughout the experiment with continuous stirring.    -   After 20 minutes, the surface of the skin was examined. If the        skin was wet or showed signs of “sweating”, the SC was        considered compromised and discarded.

Membrane Integrity Check: Once the cells had been assembled and the skinallowed to hydrate for 20 minutes, the barrier integrity of each skinsection was tested using a tritiated water test prior to the dosing ofthe formulation to the skin. The specific method for measuring skinbarrier integrity is outlined as follows and detailed in Tioga ResearchSOP Lab.011.

-   -   An aliquot of 150 μl of tritiated water (spiked with 25 μCi        water/10 ml water) was added to each FDC donor well.    -   After 5 minutes, the tritiated water from the donor wells was        removed and the skin tapped dry using a Kimwipe.    -   The receptor wells were agitated for an additional 1 hour after        the tritiated donor fluid was removed.    -   After 1 hour of agitation, a 300 μl aliquot sample was taken        from each receptor well. The remaining receptor fluid was        discarded and replaced with fresh PBS (membrane integrity study        uses only PBS in receptor fluid)    -   600 μl of scintillation cocktail (Ultima Gold XR) was added to        each sample aliquot.    -   The tritium content of the receptor-well aliquot was then        measured using a liquid scintillation counter (LSC).    -   After LSC analysis was complete, results were analyzed. Any FDCs        showing anomalously high water flux were discarded.    -   The FDCs were then ranked according to ³H water flux. The FDCs        were then distributed such that each formulation was assigned to        FDCs with nearly equivalent average tritiated water flux values.    -   Once the membrane integrity check study was complete, the entire        receptor chamber volume was replaced with the receptor fluid.

Formulation application procedure: After the membrane integrity test wascomplete, and the cells appropriately sorted, the formulations wereready to be applied to the stratum corneum of the skin. The donor cellwas first removed from the FDC—this step was necessary to allow forproper dosing of the formulations across the exposed surface area. Next,a plastic washer with a ˜0.55 cm² opening was placed on top of thecadaver skin such that the opening aligned with the receptor chamber. Aone-time dosing regimen was then used for this study. For dosingprotocol #1, 5 μl of the TA was applied to the skin and spread acrossthe skin surface using a glass rod (care was taken to ensure theformulation stayed within the confines of the plastic gasket). Fordosing protocol #2, 5 μl of the TA was applied to the skin, then spreadusing a glass rod. 5 μl of formulation P1-016 was then applied on top ofthe TA and spread, followed lastly by 5 μl of formulation P2-004 beingapplied on top of both formulations and spread across the 0.55 cm²surface area. For dosing protocol #3, 5 μl of the formulation P1-027 wasapplied to the skin, and spread using a glass rod, followed by 5 μl offormulation P2-004 being applied on top of P1-027. In all dosingprotocols, the weight of the FDC was measured before and after eachdosing step to ascertain the amount of formulation that remained afterspreading. The dose of the Active per cell and corresponding dosingprotocol is shown.

TABLE 77 Triamcinolone dose per cell for each formulation combination.The triamcinolone dose assumes a specific gravity of 1.0 for theformulation and that 100% of the 5 μl dose remains on the skin afterspreading the formulation. wt/wt % Nominal Triamcinolone DosingTriamcinolone formulation Acetonide Protocol Formulations Acetonide doseper cell dose per cell Protocol 1 TA 0.1 wt % (in TA) 5 μl 9.09 μg/cm²Protocol 2 TA + P1-016 + P2-004 0.1 wt % (in TA) 5 μl + 5 μl + 5μl 9.09μg/cm² Protocol 3 P1-027 + P2-004 0.1 wt % (in P1-027) 5 μl + 5 μl 9.09μg/cm²

Sampling of the Receptor Fluid: At 1, 2, 4, 6, 8 and 24 hours, a 300 μlsample aliquot was drawn from the receptor wells using a graduatedHamilton type injector syringe. Fresh receptor medium was added toreplace the 300 μl sample aliquot. The samples were then filtered with a0.2 μm GHP membrane filter plate.

Tape Stripping and Heat Splitting: At 24 hrs, the skin was tapped dryusing a PBS/EtOH soaked KimWipe. Next, a piece of Mepitac tape wasapplied to the skin, allowed to sit for ten minutes, then removed. ThisMepitac step was done a second time to ensure the formulation film isentirely removed. After the second Mepitac tape is removed, the skin wassuccessively tape stripped. This involved applying a piece of cellophanetape to the skin with light pressure, then peeling the tape off andcollecting the tape. With each tape strip, a layer of the stratumcorneum is removed. Nine tape strips were taken per cell. The tapestrippings were binned together in the following sections: Tape strip 1,tape strip 2, tape strip 3, tape strip 4, tape strip 5, and tapes strips6-9.

After the skin was tape stripped, the epidermis of each piece of skinwas then separated from the underlying dermal tissue using tweezers. Theepidermal and dermal tissues were collected and separately placed in to4 ml borosilicate glass vials.

After all the tape strips and skin pieces were collected, the Active wasthen extracted from the tape strips or skin. For the tape strips, thisconsisted of adding 4 ml of methanol to the vial, and agitating the vialfor 24 hours at room temperature, after which a sample was collected.For the skin pieces, extraction was carried out by adding 2 ml ofdimethyl sulfoxide (DMSO) to the vials containing the skin pieces, thenincubating the vials at 40° C. for 24 hours with gentle agitation. After24 hours, sample aliquots were taken and filtered with the 0.20 μm GHPmembrane filter plate.

Analysis of Sample: Sample aliquots were analyzed with an Agilent G6120HPLC system with a LC-MS detector. Samples were stored refrigerated at4-8° C. prior to analysis to help prevent any unwanted degradation oftriamcinolone acetonide.

Comparative delivered doses of triamcinolone for the differentformulations for transdermal, stratum corneum (i.e. tapestrips) andepidermal and dermal delivery were reported. It appears that theaddition of P1-016 and P2-004 on top of the TA (Versa Pharmaformulation) increased the flux of the triamcinolone into the deepertissue versus applying the TA from Versa Pharma formulation by itself.Dosing the skin with P1-027 and with P2-004 layered on top, led to thehighest epidermal uptake. Results are shown in FIG. 16.

Example 87 Clinical Evaluation of In-Vivo Occlusion Benefit in EnhancingSteroid Potency Via Vasoconstriction Assay

Clinical Study to evaluate in-vivo occlusion benefit in enhancingsteroid potency was adapted from traditional vasoconstriction singlepoint assay due to the presence of the film layer. The study was basedon 37 healthy volunteers (23 females and 14 males) with normal skin. Thetest articles were applied by technician on volar forearm site at 6 testsites per subject in order to test three steroids of increasing potency,comparing the vasoconstriction outcome of the steroids with the presenceversus the absence of P1-016/P2-024 film occlusion: TriamcinoloneAcetonide (TA) lotion, 0.1%—Class 5, Fluticasone Propionate (FP) lotion,0.05%—Class 5, Hydrocortisone (HC) 2.5% solution—Class 7. Thevasoconstriction readouts were reported at 18 hours without wash-off at16 hours.

Methodology: Single center, evaluator-blinded, randomized withinsubject, vehicle and reference controlled visual assessment.

Subjects: 36 planned, 37 enrolled, 37 analyzed (ITT population), 36analyzed (PP population).

-   -   Diagnosis and main criteria for inclusion: Healthy male or        female subjects 18-65 years of age with skin on the forearms        that allowed vasoconstriction to be readily assessed and have a        history or documentation of a positive skin-blanching response        to topical corticosteroids.

Duration of Treatment: Single application for 16 (±1) hours of thefollowing steroids, administered with and without occlusion usingP1-016/P2-004 film:

1. Triamcinolone Acetonide lotion, 0.1% (Class 5)

2. Fluticasone Propionate lotion, 0.05%, (Class 5)

3. Hydrocortisone solution, 2.5% (Class 7)

Criteria for Evaluation:

-   -   Efficacy: Degree of skin blanching assessed visually on a        four-point ordinal scale ranging from 0 (none) to 3 (marked        blanching).    -   Safety: All adverse events (AEs) reported during the study were        to be listed, documenting course, severity, and outcome.

Statistical Methods: Data was entered using double entry method usingExcel. All statistical processing was performed using SAS®, version 9.4.Since this was a within-subject design, demographic characteristics suchas gender and race were summarized as frequency distributions, while agewas summarized as a mean and standard deviation.

-   -   Study Populations: All subjects enrolled in the study who were        randomized and had at least one test article applied were        included in the analysis of safety and efficacy. This was the        intent-to-treat (ITT) population. Subjects were included in the        per-protocol (PP) population efficacy analyses if they completed        the study without significant protocol deviations.    -   Efficacy Analyses: The sums and means of the skin blanching        scores for each test article, with or without occlusion, were        calculated. All statistical tests were performed at a        significance level of 5% (two-tailed).        -   The primary analysis tests the null hypothesis that the            visually assessed treatment blanching score means were equal            to each other. Since this was a within-subject design, the            visual skin blanching data was analyzed for mean differences            among treatments using a randomized blocks analysis of            variance (ANOVA) with subject as the blocking variable.        -   Within this analysis, pairwise comparisons of the mean            visual assessment scores was performed using the            Ryan-Einot-Gabriel-Welsch Multiple Range Test (REGWQ) which            controls the experiment wise Type I error rate at 5% under            the complete null hypothesis. The null hypothesis states            that the treatment blanching score means are equal to each            other.    -   Safety Analyses: All AEs reported during the study were to be        listed, documenting course, severity, and relationship to test        articles and outcome. All reported AEs were to be summarized by        the number of subjects reporting AEs, system organ class (SOC),        preferred term (PT), severity and relationship to test article        by treatment, if possible.

Clinical Results

Summary of Results: Thirty-seven subjects were enrolled and treated inthe study. All but one enrolled subject (Subject 01-106) completed thestudy (N=36). There were 24 (64.9%) females and 13 (35.1%) malesenrolled into the study. Approximately 86% ( 32/37) of subjects wereWhite, 8.1% ( 3/37) were Asian and the remaining two subjects wereAmerican Indian/Alaskan Native ( 1/37, 2.7%) and White and Black/AfricanAmerican ( 1/37, 2.7%). About two-thirds of subjects were not ofHispanic or Latino origin ( 25/37, 67.6%). The average age was 34.2years with subject ages ranging from 19 to 62 years. All but one of thesubjects (Subject 01-106) cleansed the test sites within the specifiedtime windows, had the film removed, and had the vasoconstrictionassessments performed within the specified time windows. Subject 01-106was included in the ITT population but excluded from the PP population.This subject did not have the vasoconstriction assessments; thus, wasnot included in the vasoconstriction assessments summary.

-   -   Efficacy Results: Fluticasone propionate lotion, 0.05% (Class 5)        with occlusion and triamcinolone acetonide 0.1% lotion (Class 5)        with occlusion were not statistically significantly different        from each other but were statistically significantly different        from triamcinolone and fluticasone without occlusion,        hydrocortisone (Class 7) with and without occlusion.        Triamcinolone without occlusion was statistically significantly        different from all other products as was hydrocortisone without        occlusion. Hydrocortisone with occlusion and fluticasone without        occlusion were not statistically significantly different from        each other.    -   Safety Results: No subject experienced an AE and no subject        discontinued the study due to safety reasons.

TABLE 78 Clinical evaluation of in-vivo occlusion benefit in enhancingsteroid potency via GROUPING TREATMENT MEAN (REGWQ) FP lotion, 0.05%(Class 5) with P1-016/P2-024 2.44 A TA lotion, 0.1% (Class 5) withP1-016/P2-024 2.28 A TA lotion, 0.1% (Class 5) without Occlusion 1.56 BHC 2.5% solution (Class 7) with P1-016/P2-024 1.11 C FP lotion, 0.05%(Class 5) without Occlusion 0.94 C HC 2.5% solution (Class 7) withoutOcclusion 0.31 D

Clinical Conclusion

The vasoconstriction assessment results for the ITT and PP populationswere essentially the same because one subject in the ITT population didnot have the assessment. The Class 5 fluticasone and triamcinolonereference lotion products with occlusion from P1-016/P2-004 were notstatistically different from each other and were statisticallysignificantly different (more potent) than all the other referenceproducts (with occlusion from P1-016/P2-004 or without occlusion). TheClass 5 triamcinolone reference product without occlusion wasstatistically significantly different (more potent) than the Class 7(hydrocortisone) reference product (with occlusion from P1-016/P2-004 orwithout occlusion) and the Class 5 reference product fluticasone withoutocclusion. This result is somewhat different that the published potencyrating of fluticasone and triamcinolone lotion products which areidentical (i.e. Class 5 potency). Such variability however is notunanticipated in VCA from time to time. The Class 7 hydrocortisonereference product with occlusion from P1-016/P2-004 and the Class 5fluticasone reference product without occlusion were not statisticallydifferent from each other and statistically significantly different(more potent) than the Class 7 reference product without occlusion. TheClass 7 hydrocortisone reference product was statistically significantlydifferent (less potent) than all other reference products.

These results consistently demonstrated an increase in potency basedupon occlusion from P1-016/P2-004 film for all three tested RLDs. Withrespect to P1-016/P2-004 film occluded hydrocortisone 2.5% test product,the equivalency to the fluticasone lotion RLD implies an increase to aClass 5 potency from Class 7 due to occlusion with the P1-016/P2-004film. Similarly, both the Class 5 fluticasone lotion 0.05% andtriamcinolone lotion 0.1% occluded reference products were more potentthan their un-occluded counterpart. This implies an increase from Class5 potency to at least Class 4 to Class 3 potency.

Example 88 Evaluation of Clinical Efficiency for Management ofConditions of Compromised Skin Barrier Function

Evaluation of clinical efficiency for management of specific conditionsof compromised skin barrier function by application of the compositionsdisclosed herein are described below.

Subjects:

A number of subjects suitable for statistical analysis (e.g., 24 to 64)with a specific condition of compromised skin barrier function (e.g.,atopic dermatitis, psoriasis, eczema, ichthyosis vulgaris, xeroderma,rosacea) are selected for the study. For example, subjects with atopicdermatitis or eczema are selected based upon the widely acceptedcriteria proposed by Hanifin and Rajka, Diagnostic features of atopicdermatitis, Acta. Derm Venereol Suppl (Stockh) 1980; 92: 44-47. Subjectswith ichthyosis vulgaris are selected based upon the widely acceptedcriteria described in Williams et al., The U.K. Working Party'sDiagnostic Criteria for Atopic Dermatitis. III. Independent hospitalvalidation, Br J Dermatol 1994; 131(3):406-416. Anyone with marks,scars, scratches or any skin condition are NOT excluded.

Subjects are evaluated for the severity of their specific skin conditionfollowing their arrival at the test site by a dermatologist and arefollowed up during their 2 week test period, preferably by the samedermatologist. Subjects are interviewed about the duration of the skincondition, other atopic disorders including asthma or allergic rhinitis,and other seasonal difference in the specific skin condition severityand their treatment history such as steroids, moisturizer or oralanti-histamines. Subject questionnaires are also given to subjects forself-evaluations on severity of conditions and life quality such assleep pattern. Subjects may be further classified into mild, moderateand severe conditions.

Inclusion Criteria:

-   -   1. Male and female at any age (e.g., for atopic dermatitis),        between 6 and 70 years of age (e.g., for eczema, ichthyosis        vulgaris), or between 18 and 70 years of age (e.g., for        psoriasis);    -   2. Agrees to refrain from exercising and/or drinking hot or        caffeinated beverages during the 2 hours prior to their        appointment on the day of testing (this may affect the        measurements);    -   3. Is willing and able to follow all study requirements and        restrictions; and    -   4. Is able to read, understand, and sign the consent form.

Exclusion Criteria:

-   -   1. Is pregnant, nursing or planning a pregnancy as determined by        interview;    -   2. Is currently going through menopause (i.e., experiencing hot        flashes);    -   3. Is a smoker;    -   4. Any other condition or factor the Investigator or his duly        assigned representative believes may affect the skin response or        the interpretation of the test results.

Subjects are NOT instructed to stop the use of all moisturizing products(soaps, lotions, sunscreens, insect repellent, etc.) during a 3 daypre-conditioning period prior to testing which is usually instructed tofollow for regular hydration studies. However, subjects are instructednot to exercise or drink hot or caffeinated beverages within 2 hoursprior to their day of testing visit as this may affect the measurements.Subjects are instructed not to apply ointment or oil prior to theexamination.

Treatments and Procedures:

Two to six 5 cm by 5 cm test sites are outlined, using a standardtemplate as guide, on the subject's skin including two or more areaswith the specific skin condition (“skin lesion”) and one or more areaswith normal looking skin using a standard template.

Test products are applied over one to four identified skin lesions andover two to three normal looking skin area. At least one, and preferablytwo, identified skin lesions are left untreated as control. The testproducts are applied once a day throughout 2 weeks daily.

An aliquot of about 0.08-0.1 mL of the test composition is dispensed toa finger wearing finger cot and then directly applied to the test area.In case of a two-part test composition, the two compositions are appliedto the same test area, with the first test composition (about 0.08 mLper 25 cm² area) applied to skin first and the second test composition(about 0.1 mL per 5 cm²) dispensed with a new finger cot and appliedover the same area treated with the first test composition by glidingmotion to coat the treated area, but not by rubbing in, to minimize themixing of the two test materials.

Product Removal before Clinical Measurements:

All the test areas are cleansed to remove the test compositions beforeclinical measurements. The remover is shaken well to be homogeneousprior to use. The remover (1.5 mL per 25 cm²) is poured onto a cottonround pad and then the wet pad is placed on the test area to remove thetest compositions.

Clinical Measurements

Clinical measurements are conducted in one or more of the followingaspects.

-   -   Disease Severity:        -   SCORAD or OSCORAD (Objective Score of Atopic Dermatitis,            European Task Force on Atopic Dermatitis, Severity scoring            of atopic dermatitis: the SCORAD index, Dermatology 1993,            186:23-31) utilizes the rule of nines with six clinical            features of atopic dermatitis disease intensity            (eythema/darkening, edema/population, oozing/crust,            excoriations, lichenification/prurigo/pruritus, and            dryness), score ranges 0-103.        -   PASI (Psoriasis Area and Severity Index, Fredriksson and            Pettersson, Severe psoriasis—oral therapy with a new            retinoid, Dermatologica 1978; 157:238-44) is based on the            quantitative assessment of three typical signs of psoriatic            lesions: erythema (redness), infiltration (thickness), and            desquamation (scaling), on a scale of 0±4, combined with the            skin surface area involved. The basis for the PASI score is            the evaluation of four separate body areas: head, trunk, and            upper and lower extremities. Scoring them separately for            erythema, infiltration, and desquamation, after establishing            the extent of skin surface involved, is time-consuming, and            may take 10±15 min even for experienced personnel. An            example scoring form is provided in FIG. 17. The PASI score            is calculated as follows:

PASI=0.1(Eh+Ih+Dh)Ah+0.3(Et+It+Dt)At+0.2(Eu+Iu+Du)Au+0.4(El+Il+Dl)Al

-   -   -   -   where E=erythema; I=infiltration; D=desquamation;                A=area; h=head; t=trunk; u=upper extremities; and                l=lower extremities

        -   CRTT (Cutaneous Resonance Running Time, Song et al.,            Decreased cutaneous resonance running time in cured leprosy            subjects, Skin Pharmacol Physiol 2009, 22:218-224 and Xin et            al., Cutaneous resonance running time varies with age, body            site and gender ina normal Chinese population, Skin Res            Technol 2010, 16: 413-421) on psoriatic lesions by            Revicometer RVM 600: A Courage-Khazaka Reviscometer RVM600            (CKelectronic GmbH, Koln, Germany) is used to measure the            CRRTs in psoriatic lesions on the extensor of forearm and            the contralateral uninvolved sites served as control. The            measurement area with this probe is 8 mm. And the acoustical            shockwave running distance is 2 mm with energy of 1.77 lJ.            Measurements are begun in the 12 o'clock position, which is            determined with the right forearms laid on the table as            described previously. Measurements are then taken clockwise            at every 1 h interval or at every 30°. These measurements            provide the CRRTs in the directions of 0-6 o'clock, 1-7,            2-8, and so on. Readings in 1-7, 2-8, 3-9, 4-10, and 5-11            o'clock direction on the left forearm are compared with            those in 5-11, 4-10, 3-9, 2-8, 1-7 o'clock direction,            respectively, on the right forearm. All subjects rested at            20-24° C., at a relative humidity of about 50-55% for 30 min            before measurements are taken.

        -   HECSI (Hand Eczema Severity Index, Held et al., The Hand            Eczema Severity Index (HECSI): a scoring system for clinical            assessment of hand eczema, Contact Dermatitis 2005,            152:302-307) is a clinical grading system of dermatitis of            the hands used to assess product tolerability. HECSI            assesses erythema, induration/papulation, vesicles and            fissuring of dermatitis of the hands and the subject's            perception of stinging, burning and itching.

        -   NESS (Nottingham Eczema Severity Score, Emerson et al., The            Nottingham Eczema Severity Score: preliminary refinement of            the Rajka and Langeland grading, Br J Dermatol 2000, 142:            288-297 and Hon et al., Validation of a self-administered            questionnaire in Chinese in the assessment of eczema            severity, Pediatr Dermatol 2003, 20:465-469) is used to            assess clinical severity.

        -   Visual analogue scale (VAS), the Investigator's Global            Assessment (IGA) and the Ichthyosis Vulgaris Area and            Severity Index (EASI), Skin Dryness (Pruritus Severity Index            Score) are also used to assess clinical severity, as            described in Lee et al., Effectiveness of acupressure on            pruritus and lichenification associated with atopic            dermatitis: a pilot trial, Acupunct Med. 2012 March;            30(1):8-11.

    -   Quality of Life: DLQI for adults (Finlay and Khan, Dermatology        Life Quality Index (DLQI)—a simple practical measure for routine        clinical use, Clin Exp Dermatol. 1994 May; 19(3):210-6) and        CDLQI for Children (Lewis-Jones and Finlay, The Children's        Dermatology Life Quality Index (CDLQI): initial validation and        practical use, Br J Dermatol. 1995 June; 132(6):942-9)        questionnaires are used to measure how much a subject's disease        had affected their lives over the last weeks. The response to        each questionnaire was defined as 0-3 (0=not at all affected;        3=very much affected). DLQI was summarized under six subscales:        “Symptoms and feelings;” “Leisure;” “Personal relationships;”        “Treatment;” “Work and school;” and “Daily activities.” The        CDLQI was summarized under six subscales: “Symptoms and        feelings;” “Leisure;” “Personal relationships;” “Treatment;”        “School or holidays;” and “Sleep.” Total quality of life (QOL)        score was calculated by summing the score of each question.        Total QOL score and the six subscales were expressed as a        percentage of the respective maximum scores. The reliability and        validity of DLQI were assured in the review by Basra et al.,        Dermatology Life Quality Index 1994-2007: a comprehensive review        of validation data and clinical results, Br J Dermatol. 2008        November; 159(5):997-1035.

    -   Transepidermal Water Loss: TEWL and Skin Conductance or        Capacitance (Yamamoto Y, Measurement and analysis of skin        electrical impedance, Acta Derm Venereol Suppl (Stockh), 1994;        185:34-8)

    -   Stratum Corneum Integrity and Cohesion: Tape stripping is used        as the quantification of the number of sequential D-squame tape        stripping required to increase TEWL by 20 g/m² per hour

    -   Stratum Corneum Thickness: Stratum corneum thickness is        calculated from low-frequency susceptance and high-frequency        admittance by the corneometer as (square root of low-frequency        susceptance)/(high-frequency admittance²). Stratum corneum        thickness is also visualized by conventional        inmmunohistostaining. Stratum corneum thickness is also measured        using light microscopy, such as Confocal Tandem Scanning        Microscope (TSM), to measure the in depth (200 uM) measurement        of the thickness of the different skin layers.

    -   Skin Biopsy/Immunohistochemical Staining: Immunoperoxidase        staining of paraffin-embedded sections is performed using the        ChemMate Peroxidase/DAB system (Dako Cytomation, Hamburg,        Germany) to visualize the stratum corneum and epidermal        structure, epidermal thickness and extracellular lamellar        membranes.        -   Epidermis cell proliferation and hyperplasia can be examined            using immunohistochemical staining of PCNA, Ki67, Ki-S3, or            other proliferation markers.        -   Epidermal differentiation can be examined using            immunohistochemical staining of Involucrin, Keratins CK            5,6,17, 1, 5, 10, 14 or other differentiation markers

    -   Laboratory Tests: Peripheral blood EOS count (number 100 per ml;        normal 40-440), serum LDH (IU l⁻¹; normal 119-229), total serum        IgE (IU ml⁻¹; normal 0.0-400.0), and allergen-specific IgE (SRL        Inc., Tokyo, Japan) are measured. Allergen-specific IgE were        estimated by fluoroenzyme immunoassays for house dust, mite        allergen, grass pollen (Tancy), cedar pollen, fungal allergen        (Candida), animal dander, and foods. Concerning to the        sensitivity for detection of specific IgE, 100 lumicount and        values greater than or equal to 100 lumicount are considered        positive (+).        -   In addition, serum cathelicidins (LL-37) concentration is            measured using enzyme immunoassay (Bachem, San Carlos,            Calif., USA, as described in Leung et al., Circulating LL-37            is a biomarker for eczema severity in children, J Eur Acad            Dermatol Venereol. 2012; 26:518-522). Samples are diluted            90-fold prior to measurement. The sensitivity of this assay            was 1 ng/mL.

    -   Statistical Analysis: Simple regression analyses are also used        to identify significant associations of stratum corneum        hydration, thickness, or TEWL to SCORAD or PASI. Data with        P-values less than 0.05 are evaluated as significant and        P-values less than 0.005 as highly significant. Wilcoxon rank        sum test and simple regression analyses are performed to assess        the association or correlation between different biological        markers including IgE, LDH, EOS, and the SCORAD or PASI.

TABLE 79 Clinical Endpoints and Biomarkers DERMATOSIS TYPE CLINICALENDPOINT BIOMARKER Atopic Dermatitis Cutaneous Barrier Function, SkinBiopsy/Immunohisto-chemical Homeostasis and Inflammation: staining:SCORAD/OSCORAD Epidermis cell proliferation and DLQI/CDLQI hyperplasiaTEWL/Conductance/Capacitance Epidermal differentiation Stratum CorneumIntegrity and Lamellar bodies quantity in Stratum Cohesion: Corneum (SC)and Stratum Tape Stripping Granulosum (SG) Epidermal Thickness: Lightmicroscopy or Comeometer Cellular Structure: Optical coherencetomography (OCT) - Arrangement of the collagen fibres SC and epidermallipid: Lipid content Ceramide quantity: mRNA levels of the epidermalglucosylceramide transport protein (ATP-binding cassette A12) SC andepidermal protein Filaggrin (FLG) Aquaporin (AQP3) Protease activatedreceptor-2 (PAR-2) Caveolin-1 (cav-1) Skin Surface pH SC Integrity andCohesion: Skin Biopsy Serine proteases (in situ zymography) Desmoglein(Western Blot) Corneodesmosome (Western Blot) B-glucocerebrosideactivity (Western Blot) Lipid processing (SEM) Inflammation (Bloodsamples): Immunoglobulin E (IgE) Mast cell hyperactivity Dendritic cellsignalling Psoriasis Cutaneous Barrier Function and Same as AtopicDermatitis, but does Homeostasis: not include: PASI SC and epidermalprotein: TEWL/Conductance/Capacitance Filaggrin (FLG) Self-reportedQuestionnaires Aquaporin (AQP3) CRTT on psoriatic lesions by Proteaseactivated receptor-2 (PAR-2) Revicometer RVM 600 Caveolin-1 (cav-1)Stratum Corneum Integrity and Cohesion: Tape Stripping Eczema CutaneousBarrier Function and Same as Atopic Dermatitis, and further Homeostasis:includes: SCORAD/OSCORAD Expression of antimicrobial peptidesTEWL/Conductance/Capacitance Serum cathelicidin immunoassay HECSI NESSIchthyosis Vulgaris Cutaneous Barrier Function and Same as AtopicDermatitis, but does Homeostasis: not include: Pruritus Severity IndexScore SC and epidermal protein: TEWL/Conductance/Capacitance Filaggrin(FLG) Stratum Corneum Integrity and Aquaporin (AQP3) Cohesion: Proteaseactivated receptor-2 (PAR-2) Tape Stripping Caveolin-1 (cav-1) XerodermaCutaneous Barrier Function and Same as Atopic Dermatitis, but doesHomeostasis: not include: Pruritus Severity Index Score SC and epidermalprotein: TEWL/Conductance/Capacitance Filaggrin (FLG) Stratum CorneumIntegrity and Aquaporin (AQP3) Cohesion: Protease activated receptor-2(PAR-2) Tape Stripping Caveolin-1 (cav-1)

Example 89 Evaluation of Clinical Efficiency for Adult with Eczema

Evaluation of clinical efficiency for management of eczema byapplication of the compositions disclosed herein are described below.The study was a single center, open label study.

Subjects:

10 subjects (7 females and 3 males) aged 18 years and older with mild tosevere eczema including atopic dermatitis (Investigator's GlobalAssessment [IGA] Disease Severity of Grade 2 to 4)

Subjects are evaluated for the severity of their specific skin conditionfollowing their arrival at the test site by a dermatologist andparticipate in the study for five (5) days followed by an open label useperiod of up to a total of 30 days. Subjects are interviewed about theduration of the skin condition.

Inclusion Criteria:

-   -   1. Subject is a male or non-pregnant female, aged 18 years of        age or older at the time of consent.    -   2. Women of of childbearing potential (WOCBP) must have a        negative urine pregnancy test (UPT) at Visit 1/Baseline to        qualify; female subjects who are post-menopausal,¹ unable to        conceive due to previous obstetric surgery or are using an        effective method of contraception.    -   3. Subject is willing and able to give written informed consent.    -   4. Subject has the clinical diagnosis of “Eczema” which shall        include Atopic Dermatitis (AD) based upon the criteria of        Hanifin and Rajka or other forms of eczematous dermatitis in the        opinion of the investigator (e.g. nummular eczema etc.).    -   5. Subject has a clinical diagnosis of stable [within three (3)        months] mild to severe (Grade 2 to 5) Eczema as determined by        the Investigator's Global Assessment (IGA) within the designated        Treatment Area, which includes a minimum of 0.5% BSA of active        disease.    -   6. Subject is willing and able to apply the test articles(s) as        directed, comply with study instructions, and commit to all        follow-up visits for the duration of the study.    -   7. In the investigator's opinion, subject is in good general        health and is free of any disease state or physical condition        that exposes the subject to an unacceptable risk by study        participation or impairs the evaluation of the subject or test        article by participating in the study.

Exclusion Criteria:

-   -   1. Subject is pregnant, lactating, or is planning to become        pregnant during the study.    -   2. In the opinion of the investigator, the subject has skin        pathology or condition that could interfere with the evaluation        of the test products or requires the use of interfering topical        or systemic therapy during the study.    -   3. Subject has used any of the following topical preparations on        the Treatment Area:        -   a. Topical (including OTC products) treatments including,            but not limited to, corticosteroids, immunomodulators            (tacrolimus, pimecrolimus, etc.), tar, calcipotriene or            other vitamin D preparations, antihistamines (doxepin,            diphenhydramine, etc.), or antibiotics within one (1) week            of Visit 1/Baseline. Note: Stable (>30 days) doses of oral            or intranasal antihistamines for treatment of allergic            rhinitis, inhaled or intranasal corticosteroids for            treatment of bronchial asthma, or antibiotics for treatment            of acne will be allowed, but must be documented.        -   b. Retinoids (including tazarotene, adapalene, and            tretinoin) within four (4) weeks of Visit 1/Baseline.        -   c. Light treatments (PUVA, UVB, excimer laser, etc.),            microdermabrasion, or chemical peels within four (4) weeks            of Visit 1/Baseline.        -   d. Other topical therapy, which may materially affect the            subject's atopic dermatitis in the opinion of the            investigator.    -   4. Subject has used any of the following systemic medications:        -   a. Corticosteroids (including intramuscular and            intralesional injections) within one (1) week of Visit            1/Baseline.        -   b. Immunomodulators (including leukotriene) or            antimetabolites within one (1) weeks of Visit 1/Baseline.        -   c. Oral or topical Antibiotics (OTC or prescription) within            one (1) week, unless on a stable dose for acne (more than 3            months of use), of Visit 1/Baseline.        -   d. Other systemic therapy, which may materially affect the            subject's atopic dermatitis in the opinion of the            investigator.    -   5. Subject is currently using or has used an investigational        drug or investigational device treatment within 30 days of Visit        1/Baseline.    -   6. Subject is currently enrolled in an investigational study.    -   7. Subject has a history of sensitivity to any of the        ingredients in the test articles (see Section 5.1 in the        protocol).    -   8. Subject is known to be noncompliant or is unlikely to comply        with the requirements of the study protocol (e.g., due to        alcoholism, drug dependency, mental incapacity) in the opinion        of the investigator.    -   9. Subject currently has a skin infection.

Treatments and Procedures:

The study will consist of three (3) clinic visits over five (5) days andtwo follow-up visits on Day 15 (visit 4) and Day 30 (visit 5).

Visit 1 (Screening/Baseline): Day 1. Subjects can be screened for thestudy up to 30 days before Visit 1. During screening, the studyrequirements will be reviewed, written informed consent obtained, andeligibility confirmed. If applicable, the washout from prohibitedmedications or treatments will be determined and implemented. Theseprocedures may be performed as a separate screening visit prior to theBaseline Visit, as/if required.

Demographics, inclusion/exclusion criteria, medical/dermatologicalhistory, and concomitant medications and therapies will be reviewed todetermine subject eligibility. A brief dermatologic exam and UPT (ifapplicable) will be performed. Clinical evaluations (IGA and ClinicalSigns of Eczema) and itch assessment will be performed prior to testarticle application. The Treatment Area will be defined as a discretecontiguous anatomic unit of up to 3% BSA (e.g., an arm, leg, abdomen,etc.), which must include a minimum of 0.5% BSA of active disease. Thepercent BSA to be treated and the location of the Eczema affected skinwill be documented. The percent BSA will be estimated based on theassumption that 1% BSA is equivalent to the area of the subject's handwith fingers held together.

The test article will be applied to the Treatment Area using thefollowing instructions:

1. Wash with an antimicrobial soap and completely dry the affected area.

2. Use a clean and dry fingertip to dispense and apply a thin layer ofP1-016 formulation to the Treatment Area. Ensure the product is in auniform layer with no thick areas. Approximately a quarter-sized amountof P1-016 should cover 1% BSA.

3. Clean your fingertip.

4. Use a fingertip to dispense and apply a thin layer of P2-004formulation. Gently spread the P2-004, completely covering the P1-016area. Do not rub into the P1-016 layer; simply glide until it is evenlysitting on top. 1-1.5X amount of P2-004 can be used compared to P1-016.Approximately a quarter-sized amount of P2-004 should cover 1% BSA.

5. Do not touch or move for at least 2 minutes while film sets.

Photographs may be taken to document the baseline Treatment Area. Thesubject will be asked about his/her impression of the product and itsease of use; responses will be documented in a subject questionnaire.Any AEs will be documented.

Use of topical Eczema care of affected skin areas outside of theTreatment area is allowed during the study period. Systemic Eczematreatments or other topical treatments of any kind in the Treatment Areaare prohibited.

Test article and a diary will be provided to the subject prior todischarge from the clinic. These materials will be returned by thesubject to the site at the next clinic visit. The subject will beinstructed to apply the film each day, as needed, until the next clinicvisit; if the film remains intact throughout the day no furtherapplication is needed until the film starts to peel off or break down.As required, the subject may apply the film up to twice daily asdesignated by the investigator to maintain an intact film on theTreatment Area. In most cases, it is anticipated that the subject willbe applying the film every 1 to 3 days, depending on how well it wears.Prior to each application of the film, the old film will be removed asdirected per protocol. At the request of the investigator, as an option,during any clinic visit the film may be removed and reapplied by thesubject under supervision rather than at home. In all cases, during thestudy, the subject will document apply applications of the film in thesubject diary provided. The subject will be scheduled for their nextreturn visit and discharged from the clinic.

Visit 2 (Follow-Up): Day 3±1 day. Subjects will return to the clinic forfollow-up and queried for any changes in health status. Concomitantmedications will be reviewed. Clinical evaluations (IGA and ClinicalSigns of Eczema) and P1-016/P2-004 Film durability and itch assessmentswill be performed. Photographs may be taken to document the durabilityof the treatment. Any AEs will be documented.

Test article and a diary will be reviewed and, as required, new testarticle and/or a new diary will be provided by the subject prior todischarge from the clinic. These materials will be returned by thesubject to the site at the next clinic visit. The subject will beinstructed to apply the film each day, as needed, until the next clinicvisit; if the film remains intact throughout the day no furtherapplication is needed until the film starts to peel off or break down.As required, the subject may apply the film up to twice daily asdesignated by the investigator to maintain an intact film on theTreatment Area. In most cases, it is anticipated that the subject willbe applying the film every 1 to 3 days, depending on how well it wears.Prior to each application of the film, the old film will be removed asdirected per protocol. At the request of the investigator, as an option,during any clinic visit the film may be removed and reapplied by thesubject under supervision rather than at home. In all cases, during thestudy, the subject will document apply applications of the film in thesubject diary provided. The subject will be scheduled for their nextreturn visit and discharged from the clinic.

Visit 3 (End of Film Durability Assessment): Day 5±1 day. Subjects willreturn to the clinic for follow-up and queried for any changes in healthstatus. Concomitant medications will be reviewed. Clinical evaluations(IGA and Clinical Signs of Eczema) and P1-016/P2-004 Film durability anditch assessments will be performed. Photographs may be taken to documentthe durability of the treatment. The subject will be instructed on howto remove the film and removal will occur in the clinic undersupervision from the study staff. The ease of film removal and anyrelated irritation of the skin will be noted. The subject will be askedabout his/her impression of the product and its ease of use; responseswill be documented in a subject questionnaire. Any AEs will bedocumented.

Test article and a diary will be reviewed and, as required, new testarticle and/or a new diary will be provided by the subject prior todischarge from the clinic. These materials will be returned by thesubject to the site at the next clinic visit. The subject will beinstructed to apply the film each day, as needed, until the next clinicvisit; if the film remains intact throughout the day no furtherapplication is needed until the film starts to peel off or break down.As required, the subject may apply the film up to twice daily asdesignated by the investigator to maintain an intact film on theTreatment Area. In most cases, it is anticipated that the subject willbe applying the film every 1 to 3 days, depending on how well it wears.Prior to each application of the film, the old film will be removed asdirected per protocol. At the request of the investigator, as an option,during any clinic visit the film may be removed and reapplied by thesubject under supervision rather than at home. In all cases, during thestudy, the subject will document apply applications of the film in thesubject diary provided. The subject will be scheduled for their nextreturn visit and discharged from the clinic.

Visits 4 (Follow-Up): Day 15±2 days. Subjects will return to the clinicfor follow-up and queried for any changes in health status. Concomitantmedications will be reviewed. Clinical evaluations (IGA and ClinicalSigns of Eczema) and P1-016/P2-004 Film durability and itch assessmentswill be performed. Photographs may be taken to document the durabilityof the treatment. Any AEs will be documented.

Test article and a diary will be reviewed and, as required, new testarticle and/or a new diary will be provided by the subject prior todischarge from the clinic. These materials will be returned by thesubject to the site at the next clinic visit. The subject will beinstructed to apply the film each day, as needed, until the next clinicvisit; if the film remains intact throughout the day no furtherapplication is needed until the film starts to peel off or break down.As required, the subject may apply the film up to twice daily asdesignated by the investigator to maintain an intact film on theTreatment Area. In most cases, it is anticipated that the subject willbe applying the film every 1 to 3 days, depending on how well it wears.Prior to each application of the film, the old film will be removed asdirected per protocol. At the request of the investigator, as an option,during any clinic visit the film may be removed and reapplied by thesubject under supervision rather than at home. In all cases, during thestudy, the subject will document apply applications of the film in thesubject diary provided. The subject will be scheduled for their nextreturn visit and discharged from the clinic.

Visits 5 (End of Study, or Early Termination): Day 30±3 days. Subjectswill return to the clinic for follow-up and queried for any changes inhealth status. Concomitant medications will be reviewed. A UPT (ifapplicable) will be performed. Clinical evaluations (IGA and ClinicalSigns of Eczema) and P1-016/P2-004 Film durability and itch assessmentswill be performed. Photographs may be taken to document the durabilityof the treatment. The film will be removed. Test article and diary willbe collected. Any AEs will be documented. The subject will be dischargedfrom the study.

Two to six 5 cm by 5 cm test sites are outlined, using a standardtemplate as guide, on the subject's skin including two or more areaswith the specific skin condition (“skin lesion”) and one or more areaswith normal looking skin using a standard template.

Test products are applied over one to four identified skin lesions andover two to three normal looking skin area. At least one, and preferablytwo, identified skin lesions are left untreated as control. The testproducts are applied once a day throughout 2 weeks daily.

An aliquot of about 0.08-0.1 mL of the test composition is dispensed toa finger wearing finger cot and then directly applied to the test area.In case of a two-part test composition, the two compositions are appliedto the same test area, with the first test composition (about 0.08 mLper 25 cm² area) applied to skin first and the second test composition(about 0.1 mL per 5 cm²) dispensed with a new finger cot and appliedover the same area treated with the first test composition by glidingmotion to coat the treated area, but not by rubbing in, to minimize themixing of the two test materials.

Clinical Measurements

Efficacy: Efficacy will be assessed in the Treatment Area at everyvisit.

Investigator's Global Assessment (IGA): Overall severity of atopicdermatitis or Eczema using a 6-point ordinal scale from 0=clear to5=very severe. This is a static morphological scale that refers to apoint in time and not a comparison to Baseline.

Clinical Signs of Atopic Dermatitis/Eczema: The severity of theindividual signs of AD or Eczema (erythema, induration/papulation,excoriation, lichenification, and oozing/crusting) using a 5-pointordinal scale from 0=none to 4=severe.

Safety: All AEs and concomitant medications will be recorded at eachvisit.

P1-016/P2-004 Film durability (Visits 2-5) and itch (Visits 1-5) will beassessed (i) as the percent BSA remaining of the test article film, (ii)by questionnaire and (iii) by photographs (optional) to document focalareas of integrity of the film at the discretion of the investigator.

The Durability Questionnaire will contain the following questions:

(1) the test article peeled from the Treatment Area: (a) not at all, (b)a slight amount, (c) a moderate amount, or (d) a large amount (at Visits2-5, prior to film removal);

(2) the test article flaked from the Treatment Area: (a) not at all, (b)a slight amount, (c) a moderate amount, or (d) a large amount (at Visits2-5, prior to film removal);

(3) the test article now covers (a) 0-25%, (b) 25.1-50%, (c) 50.1-75%,(d) 75.1-85%, or (e) 85.1-100% of the original Treatment Area coveredwith the film at the Baseline visit (at Visits 2-5, prior to filmremoval);

(4) the film removal process resulted in skin irritation in theTreatment Area: (a) not at all, (b) a slight amount, (c) a moderateamount, or (d) a large amount (at Visits 2-5);

(5) the test article lasted between treatment days, on average, for: (a)12 hours or less or (b) 12-24 hours (at Visits 2-5); NOTE: this questionto be answered by subject.

(6) How would you rate the degree of itch in the Treatment Area over thepast 24 hours: 0=none, 1=a trace, 2=mild; 3=moderate; 4=severe? (atVisits 1-5 m, prior to Visit 1 application or film removal) NOTE: thisquestion to be answered by subject.

Other Assessments: Subjects will complete a Subject Questionnaire todocument his/her impression of the product and its ease of use at Visit3 and Visit 5/End of Study.

The Subject Questionnaire will contain the following questions:

(1) overall satisfaction with the study product: (a) excellent [verysatisfied], (b) good [moderately satisfied], (c) fair [slightlysatisfied], and (d) poor [not satisfied at all].

(2) was the application of the study product easy to perform: (a) veryeasy, (b) moderately easy, (c) slightly easy, and (d) not easy at all.

(3) was the removal of the study product easy to perform: (a) very easy,(b) moderately easy, (c) slightly easy, and (d) not easy at all.

(4) overall the study product: (a) very significantly improved, (b)improved, (c) did not improve or worsen (no real change) or (d) worsenedthe treated areas of my skin disease.

(5) based on your experience would you consider using this product totreat your condition rather than other topical medications likesteroids: Yes/No, (free text explanation is optional) [Visit 5, EOSonly].

Study Endpoints:

Efficacy Endpoints: Atopic dermatitis severity variables (IGA andClinical Signs of Eczema) will be summarized descriptively by visit.Itch ratings from subject's questionnaire will be analyzed.

Safety Endpoint(s): Endpoints will be summarized descriptively by visit.

-   -   Incidence (severity and causality) of any local and systemic        treatment emergent AEs (TEAEs).    -   Percent BSA of test article remaining.    -   Number of subjects by response for each question of the        Durability Questionnaire.

Other Endpoints(s): Number of subjects by response for each question ofthe Subject Questionnaire.

Statistical Methods:

All statistical processing will be performed using SAS® unless otherwisestated. Summary tables (descriptive statistics and/or frequency tables)will be provided for all variables. Continuous variables will bedescribed by descriptive statistics (n, mean, median, standarddeviation, minimum, and maximum). Frequency counts and percentage ofsubjects within each category will be provided for categorical data.

-   -   Study Populations: All randomized subjects who received and        applied the test article will be included in the analysis of        safety and will be considered the Safety population. Subjects        that completed the study without significant protocol deviations        will be included in the Evaluable Population.    -   Efficacy Analyses: The efficacy analyses will be conducted on        the Evaluable population.        -   Investigator's Global Assessment: Frequency distributions of            IGA scores will be summarized by severity at each visit.        -   Clinical Signs of Eczema: Frequency distributions of each            clinical sign of Eczema will be summarized by severity at            each visit. Reduction of Itch ratings self-reported on a            scale of 0=none, 1=a trace, 2=mild, 3=moderate, 4=severe in            subject's questionnaires will be analyzed.    -   Safety Analyses: The analysis of safety will be conducted on the        Safety population.        -   Adverse Events: All AEs reported during the study will be            listed, documenting course, severity, investigator            assessment of the relationship to the test articles, and            outcome. All reported AEs will be summarized by the number            of subjects reporting AEs, SOC, PT, severity, and            relationship to test article.    -   Percent BSA of Test Article Remaining in Treatment Area:        Descriptive statistics will be used to summarize the percent BSA        of the test article remaining in the Treatment Area at each        visit.    -   Durability Questionnaire: Each question from the durability        questionnaire will be summarized by frequency and response at        each visit.    -   Urine Pregnancy Tests: UPT results (if applicable) at Baseline        will be provided in a listing.    -   Concomitant Medications and Therapies: Concomitant medications        and therapies will be provided in a listing.    -   Other Analyses: The other analyses will be conducted on the        Evaluable population.        -   Subject Questionnaire: Each question from the subject            questionnaire will be summarized by frequency and response            at each visit.

Clinical Results:

10 subjects applied P1-016/P2-004 test composition up to 2× daily to adiscrete area (0.5-3% BSA) of active disease. Female: 70%, Male: 30%.Age mean: 31.6 years

-   -   Durability on skin (% remaining): P1-016/P2-004 film was durable        on average 24-48 hours and caused little to no irritation when        removed    -   Safety: No material safety issues    -   Efficacy (via Investigator's Global Assessment and clinical        signs of atopic dermatitis): Marked improvement in overall        disease and signs/symptoms over the 30-day treatment.        Improvement of clinical signs parallels IGA improvements.        Results are also shown in FIG. 18(A-I).    -   Overall satisfaction: Majority of subjects were satisfied with        treatment and rated the study product as easy to use and remove.        88.9% of subjects were moderately or very satisfied with product        (Day 30). 88.9% of subjects found product moderately or very        easy to apply (Day 30). 88.9% of subjects would consider using        the product rather than other medications (Day 30)

While the present invention has been described with reference toexemplary embodiments, it is to be understood that the invention is notlimited to the disclosed exemplary embodiments. The scope of thefollowing claims is to be accorded the broadest interpretation so as toencompass all such modifications and equivalent structures andfunctions.

1. A composition for the in-situ formation of a layer over the skin of asubject, comprising one or more crosslinkable polymers. 2-20. (canceled)21. A composition for the in-situ formation of a layer over the skin ofa subject, wherein said composition is a two-part composition comprisinga first and a second part; wherein said first part comprises asingredients: Polymer A, which is one or more organopolysiloxane(s)having on average at least two alkenyl-functional groups and having aviscosity of about 10,000 to about 2,000,000 cSt at about 25° C.;Polymer B, which is one or more organopolysiloxane(s) having on averageat least two Si—H units and having a viscosity of about 2 to about500,000 cSt at about 25° C.; wherein said second part comprises asingredients: a catalyst that facilitates crosslinking of the Polymers Aand B; and Polymer C, which is one or more organopolysiloxane(s) havingon average at least one alkenyl-functional group and having a viscosityof about 0.7 to about 10,000 cSt at about 25° C.
 22. The composition ofclaim 21, wherein said Polymer A has an average molecular weight ofgreater than about 60,000 Da, greater than about 72,000 Da, greater thanabout 84,000 Da, greater than about 96,000 Da, greater than about100,000 Da, greater than about 140,000 Da, or greater than about 150,000Da, and wherein said Polymer A has an average molecular weight of lessthan about 500,000 Da, less than about 200,000 Da, less than about190,000 Da, less than about 180,000 Da, less than about 170,000 Da, orless than about 160,000 Da.
 23. The composition of claim 21, whereinsaid Polymer B has an average molecular weight of greater than about 400Da, greater than about 500 Da, greater than about 800 Da, greater thanabout 1,200 Da, greater than about 1,800 Da, or greater than about 2,000Da, and wherein said Polymer B has an average molecular weight of lessthan about 500,000 Da, less than about 250,000 Da, less than about140,000 Da, less than about 100,000 Da, less than about 72,000 Da, lessthan about 62,700 Da, less than about 49,500 Da, less than about 36,000Da, less than about 28,000 Da, or less than about 17,200 Da.
 24. Thecomposition of claim 21, wherein said Polymer C has an average molecularweight of greater than about 180 Da, greater than about 500 Da, greaterthan about 800 Da, greater than about 1,500 Da, greater than about 3,000Da, or greater than about 6,000 Da, greater than about 9,400 Da, andwherein said Polymer C has an average molecular weight of less thanabout 65,000 Da, less than about 50,000 Da, less than about 45,000 Da,less than about 30,000 Da, or less than about 17,500 Da.
 25. Thecomposition of claim 21, wherein said Polymer A has an average molecularweight of about 155,000 Da; and/or wherein said Polymer B has an averagemolecular weight of between about 2,200 and about 6,000 Da; and/orwherein said Polymer C has an average molecular weight of about 10,000Da.
 26. The composition of claim 21, wherein said first part comprisesas ingredients: (i) about 5 to about 90% by weight of said Polymer A;about 5 to about 75% by weight of said Polymer B; and about 0 to about25% by weight of a reinforcing component; or (ii) about 50 to about 90%by weight of said Polymer A; about 5 to about 30% by weight of saidPolymer B; and about 5 to about 15% by weight of a reinforcingcomponent.
 27. The composition of claim 21, wherein said second partcomprises as ingredients: (i) about 0.01 to about 20% by weight of saidPolymer C and about 0.005 to about 0.05% by weight of said catalyst; or(ii) about 0.5 to about 10% by weight of said Polymer C and about 0.01to about 0.03% by weight of said catalyst.
 28. The composition of claim21, wherein said first part comprises as ingredients: about 5 to about90% by weight of said Polymer A; about 5 to about 75% by weight of saidPolymer B; and about 0 to about 25% by weight of a reinforcingcomponent; and wherein said second part comprises as ingredients: about0.01 to about 20% by weight of said Polymer C and about 0.005 to about0.05% by weight of said catalyst.
 29. The composition of claim 21,wherein the molar ratio of Si—H functional group from said Polymer B toalkenyl-functional group from said Polymer A is from about 60:1 to about1:5; and/or wherein the molar ratio of Si—H functional group from saidPolymer B to alkenyl-functional group from said Polymer A is about 45:1to about 15:1; and/or wherein the molar ratio of Si—H functional groupfrom said Polymer B to alkenyl-functional group from said Polymer C isfrom about 60:1 to about 1:5; and/or wherein the molar ratio of Si—Hfunctional group from said Polymer B to alkenyl-functional group fromsaid Polymer C is about 45:1 to about 15:1; and/or wherein the molarratio of alkenyl-functional group from said Polymer A toalkenyl-functional group from said Polymer C is about 100:1 to about1:100; and/or wherein the molar ratio of alkenyl-functional group fromsaid Polymer A to alkenyl-functional group from said Polymer C is about10:1 to about 1:10.
 30. The composition of claim 21, wherein saidPolymer C is selected from vinyl terminated polydimethylsiloxane, vinylterminated diphenyl siloxane-dimethylsiloxane copolymers, vinylterminated polyphenylmethylsiloxane, vinylphenylmethyl terminatedvinylphenylsiloxane-phenylmethylsiloxane copolymer, vinyl terminatedtrifluoropropylmethylsiloxane-dimethylsiloxane copolymer, vinylterminated diethyl siloxane-dimethylsiloxane copolymer,vinylmethylsiloxane-dimethylsiloxane copolymer, trimethylsiloxyterminated, vinylmethylsiloxane-dimethylsiloxane copolymers, silanolterminated, vinylmethylsiloxane-dimethylsiloxane copolymers, vinylterminated, vinyl gums, vinylmethylsiloxane homopolymers, vinylT-structure polymers, monovinyl terminated polydimethylsiloxanes,vinylmethylsiloxane terpolymers, vinylmethoxysilane homopolymers, orcombinations thereof.
 31. The composition of claim 30, wherein saidPolymer C is vinyl dimethicone.
 32. The composition of claim 21, whereinsaid Polymer C has a viscosity of greater than about 0.7 cSt, greaterthan about 1 cSt, greater than about 6 cSt, greater than about 10 cSt,greater than about 20 cSt, greater than about 50 cSt, greater than about100 cSt, or greater than about 200 cSt at about 25° C., and wherein saidPolymer C has a viscosity of less than about 10,000 cSt, less than about5,000 cSt, less than about 4,000 cSt, less than about 2,000 cSt, lessthan about 1,000 cSt, or less than about 500 cSt at about 25° C.
 33. Thecomposition of claim 21, wherein said Polymer C has a viscosity of about250 cSt at about 25° C.
 34. A composition as defined in claim 21 for usein a method for modifying skin function, wherein the method comprisesapplying the composition to the subject in need thereof.
 35. A kitcomprising the composition of claim 21 and instructions for use.
 36. Thekit of claim 35, wherein the kit further comprises a cleanser suitablefor removing said layer from the skin; and/or one or more brush(es),swab(s), and/or mirror(s).